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Ofatumumab Added to Fludarabine-Cyclophosphamide vs Fludarabine-Cyclophosphamide Combination in Relapsed Subjects With Chronic Lymphocytic Leukemia

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ClinicalTrials.gov Identifier: NCT00824265
Recruitment Status : Completed
First Posted : January 16, 2009
Results First Posted : July 25, 2016
Last Update Posted : November 9, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Leukaemia, Lymphocytic, Chronic
Interventions Drug: OFC Infusion
Drug: FC infusion
Enrollment 365

Recruitment Details Participants (par) were screened within 14 days prior to the start of study drug administration to determine eligibility.
Pre-assignment Details Eligible par were stratified by Stage (Binet A vs. B vs. C) and number of prior therapies (1-2 vs. ≥3). Par in each stratum were then centrally randomized in a 1:1 ratio to recive intravenous (IV) fludarabine and cyclophosphamide in combination with ofatumumab or IV fludarabine and cyclophosphamide alone.
Arm/Group Title Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Fludarabine + Cyclophosphamide_ ITT Subjects
Hide Arm/Group Description Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared [m^2] and cyclophosphamide was administered at 250mg/m^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status. Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m^2 and cyclophosphamide administered at 250mg/m^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Period Title: Treatment Phase
Started 183 182
Completed 119 102
Not Completed 64 80
Reason Not Completed
Adverse Event,non-fatal             50             52
Protocol Violation             1             0
Lost to Follow-up             1             1
Physician Decision             6             12
Withdrawal by Subject             6             15
Period Title: Follow-up Phase
Started 172 160
Completed 154 129
Not Completed 18 31
Reason Not Completed
w/drew consent, no f/u, or MD choice             18             31
Period Title: Survival Follow-up Phase
Started 96 89
Completed 87 73
Not Completed 9 16
Reason Not Completed
w/drew consent, no f/u, or MD choice             9             16
Arm/Group Title Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Fludarabine + Cyclophosphamide_ ITT Subjects Total
Hide Arm/Group Description Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared [m^2] and cyclophosphamide was administered at 250mg/m^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status. Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m^2 and cyclophosphamide administered at 250mg/m^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status. Total of all reporting groups
Overall Number of Baseline Participants 183 182 365
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 183 participants 182 participants 365 participants
61.4  (8.82) 61.6  (10.21) 61.5  (9.53)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 183 participants 182 participants 365 participants
Female
79
  43.2%
66
  36.3%
145
  39.7%
Male
104
  56.8%
116
  63.7%
220
  60.3%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 183 participants 182 participants 365 participants
African American/African Heritage
3
   1.6%
5
   2.7%
8
   2.2%
American Indian or Alaska Native
3
   1.6%
1
   0.5%
4
   1.1%
Asian - Central/South Asian Heritage
13
   7.1%
16
   8.8%
29
   7.9%
Asian - East Asian Heritage
3
   1.6%
3
   1.6%
6
   1.6%
Asian - South East Asian Heritage
3
   1.6%
3
   1.6%
6
   1.6%
White - Arabic/North African Heritage
0
   0.0%
1
   0.5%
1
   0.3%
White - White/Caucasian/European Heritage
158
  86.3%
153
  84.1%
311
  85.2%
1.Primary Outcome
Title Progression-free Survival (PFS), as Assessed by the Independent Review Committee (IRC)
Hide Description PFS is defined as the interval of time between the date of randomization and the earlier of the date of disease progression (progressive disease,PD) and the date of death due to any cause. PD requires at least one of the following: lymphadenopathy, appearance of any new lesion such as enlargerd lymph nodes (>1.5 cm) spleen or liver or other infiltrates or an increase by 50% or more in the greatest diameter of any previous site; an increase by 50% or more in the previously noted enlargement of the liver or spleen, an increase by 50% or more in the numbers of blood lymphocytes with at least 5000 lymphocytes per microliter, transformation to a more aggressive histology, or occurrence of cytopenia attributable to chronic lymphocytic leukaemia (CLL).
Time Frame From randomization up to 5 years after last dose of study drug
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all participants randomized and received study drug.
Arm/Group Title Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Fludarabine + Cyclophosphamide_ ITT Subjects
Hide Arm/Group Description:
Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared [m^2] and cyclophosphamide was administered at 250mg/m^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m^2 and cyclophosphamide administered at 250mg/m^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Overall Number of Participants Analyzed 183 182
Median (95% Confidence Interval)
Unit of Measure: Months
28.94
(22.80 to 35.88)
18.83
(14.42 to 25.82)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects, Fludarabine + Cyclophosphamide_ ITT Subjects
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0032
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.67
Confidence Interval (2-Sided) 95%
0.51 to 0.88
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Overall Survival (OS)
Hide Description Overall survival is defined as the time from randomization to death due to any cause. Each participant was followed at the time when the last IRC-assessed PFS events occurred. Participants who had not died were censored at the date of last contact.
Time Frame From randomization up to 5 years after last dose of study drug
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Fludarabine + Cyclophosphamide_ ITT Subjects
Hide Arm/Group Description:
Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared [m^2] and cyclophosphamide was administered at 250mg/m^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m^2 and cyclophosphamide administered at 250mg/m^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Overall Number of Participants Analyzed 183 182
Median (95% Confidence Interval)
Unit of Measure: Months
62.65 [1] 
(44.58 to NA)
46.23
(37.72 to 56.57)
[1]
Upper limit was not able to calculate due to an insufficient number of events (high censoring rate) and high follow-up time
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects, Fludarabine + Cyclophosphamide_ ITT Subjects
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1427
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.80
Confidence Interval (2-Sided) 95%
0.59 to 1.09
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Time to Response, as Assessed by the IRC
Hide Description Time to response is defined as the time from randomization to the first response. Complete Response/remission(CR) all the criteria at least 2 months after last treatment: no lymphadenopathy(Ly) > 1.5 cm/ hepatomegaly/spleenomegaly/constitutional symptoms; neutrophils >1500 per microliter(µL), platelets(PL) >100,000/µL, hemoglobin(Hb) >11 grams/deciliter(g/dL), lymphocytes(LC) <4000/µL, bone marrow(BM) sample must be normocellular for age, <30% LC, no lymphoid nodule. Incomplete bone marrow recovery(CRi): CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. Partial Remission/response(PR): >=50% decrease in LC, Ly, size of liver and spleen and at least one of the following results: PL >100,000/µL or 50% improvement over Baseline(BL), Hb >11 g/dL or 50% improvement over BL. Nodular PR(nPR): persistent nodules BM.
Time Frame From randomization up to 5 years after last dose of study drug
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Participants with unknown or missing responses were considered as non-responders. Only responders were included in the analysis.
Arm/Group Title Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Fludarabine + Cyclophosphamide_ ITT Subjects
Hide Arm/Group Description:
Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared [m^2] and cyclophosphamide was administered at 250mg/m^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m^2 and cyclophosphamide administered at 250mg/m^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Overall Number of Participants Analyzed 152 123
Median (95% Confidence Interval)
Unit of Measure: Months
0.99
(0.95 to 1.08)
0.99
(0.95 to 1.18)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects, Fludarabine + Cyclophosphamide_ ITT Subjects
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4490
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.08
Confidence Interval (2-Sided) 95%
0.85 to 1.37
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Duration of Response (DOR), as Assessed by the IRC
Hide Description DOR is defined as the time from the initial response (CR, CRi, nPR, or PR) to the first documented sign of PD or death due to any cause. PD requires at least one of the following: lymphadenopathy, appearance of any new lesion such as enlargerd lymph nodes (>1.5 cm) spleen or liver or other infiltrates or an increase by 50% or more in the greatest diameter of any previous site; an increase by 50% or more in the previously noted enlargement of the liver or spleen, an increase by 50% or more in the numbers of blood lymphocytes with at least 5000 lymphocytes per microliter, transformation to a more aggressive histology, or occurrence of cytopenia attributable to chronic lymphocytic leukaemia.
Time Frame From time of initial response to disease progression or death, whichever came first (up to 5 years after the last dose of study drug)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Par with unknown or missing responses were considered as non-responders, only responders were included in this analysis.
Arm/Group Title Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Fludarabine + Cyclophosphamide_ ITT Subjects
Hide Arm/Group Description:
Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared [m^2] and cyclophosphamide was administered at 250mg/m^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m^2 and cyclophosphamide administered at 250mg/m^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Overall Number of Participants Analyzed 152 123
Median (95% Confidence Interval)
Unit of Measure: Months
29.63
(25.03 to 41.46)
24.90
(18.99 to 28.12)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects, Fludarabine + Cyclophosphamide_ ITT Subjects
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0878
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.56 to 1.05
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Time to Progression, as Assessed by the IRC
Hide Description Time to progression is defined as the time from the date of randomization to PD. PD requires at least one of the following: lymphadenopathy, appearance of any new lesion such as enlargerd lymph nodes (>1.5 cm) spleen or liver or other infiltrates or an increase by 50% or more in the greatest diameter of any previous site; an increase by 50% or more in the previously noted enlargement of the liver or spleen, an increase by 50% or more in the numbers of blood lymphocytes with at least 5000 lymphocytes per microliter, transformation to a more aggressive histology, or occurrence of cytopenia attributable to chronic lymphocytic leukaemia.
Time Frame From randomization up to 5 years after the last dose of study drug
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Fludarabine + Cyclophosphamide_ ITT Subjects
Hide Arm/Group Description:
Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared [m^2] and cyclophosphamide was administered at 250mg/m^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m^2 and cyclophosphamide administered at 250mg/m^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Overall Number of Participants Analyzed 183 182
Median (95% Confidence Interval)
Unit of Measure: Months
42.12
(28.94 to 47.67)
26.78
(22.51 to 31.87)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects, Fludarabine + Cyclophosphamide_ ITT Subjects
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0036
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.63
Confidence Interval (2-Sided) 95%
0.45 to 0.87
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Time to Next Therapy
Hide Description Time to next therapy is defined as the time from randomization until the start of the next-line of treatment. Data are presented for participants who took anti-cancer therapies and participants in the ITT population.
Time Frame From the start of study drug until the start of the next anti-CLL therapy (up to 5 years after the last dose of study drug)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Ofatumumab+Fludarabine+Cyclophosphamide_anti-CLL Therapies Fludarabine+Cyclophosphamide_anti-CLL Therapies Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Fludarabine + Cyclophosphamide_ ITT Subjects
Hide Arm/Group Description:
Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared [m^2] and cyclophosphamide was administered at 250mg/m^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m^2 and cyclophosphamide administered at 250mg/m^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared [m^2] and cyclophosphamide was administered at 250mg/m^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m^2 and cyclophosphamide administered at 250mg/m^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Overall Number of Participants Analyzed 74 67 183 182
Median (95% Confidence Interval)
Unit of Measure: Months
29.68
(24.97 to 32.66)
21.03
(16.79 to 28.35)
52.96
(43.56 to 62.98)
40.08
(32.85 to 48.39)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects, Fludarabine + Cyclophosphamide_ ITT Subjects
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments Participants in the ITT population
Statistical Test of Hypothesis P-Value 0.1143
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.55 to 1.08
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ofatumumab+Fludarabine+Cyclophosphamide_anti-CLL Therapies, Fludarabine+Cyclophosphamide_anti-CLL Therapies
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments Participants who took anti-cancer therapies
Statistical Test of Hypothesis P-Value 0.0109
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.67
Confidence Interval (2-Sided) 95%
0.48 to 0.94
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status
Hide Description The ECOG performance status scales and criteria are used by doctors and researchers to assess how a participant's disease is progressing, how the disease affects the daily living, and determines appropriate treatment and prognosis. ECOG performance status are measured at Cycle 2 Day1, Cycle 3 Day1, Cycle 4 Day1, Cycle 5 Day1 and Cycle 6 Day1. During follow period, 1 M after study drug therapy, then every 3 month up to 5 year (up to 60 months). Improvement is defined as a decrease from baseline by at least one step on the ECOG performance status scale (yes/no).
Time Frame Cycle 2 Day1, Cycle 3 Day1, Cycle 4 Day1, Cycle 5 Day1, Cycle 6 Day1, follow up (FU) at 1Month (M) after study drug therapy, 3M, then every 3 month up to 5 year (up to 60 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Arm/Group Title Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Fludarabine + Cyclophosphamide_ ITT Subjects
Hide Arm/Group Description:
Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared [m^2] and cyclophosphamide was administered at 250mg/m^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m^2 and cyclophosphamide administered at 250mg/m^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Overall Number of Participants Analyzed 183 182
Measure Type: Number
Unit of Measure: Participants
Cycle 2 Day 1, n= 170, 168 Number Analyzed 170 participants 168 participants
15 13
Cycle 3 Day 1, n= 165,157 Number Analyzed 165 participants 157 participants
16 13
Cycle 4 Day 1, n= 153, 132 Number Analyzed 153 participants 132 participants
19 13
Cycle 5 Day 1, n= 135, 118 Number Analyzed 135 participants 118 participants
20 15
Cycle 6 Day 1, n= 120, 96 Number Analyzed 120 participants 96 participants
26 16
1 M, FU, n= 159, 145 Number Analyzed 159 participants 145 participants
31 22
3 M, FU, n= 152, 119 Number Analyzed 152 participants 119 participants
31 21
6 M, FU, n= 136, 104 Number Analyzed 136 participants 104 participants
30 18
9 M, FU, n= 127, 96 Number Analyzed 127 participants 96 participants
31 23
12 M, FU, n= 118, 87 Number Analyzed 118 participants 87 participants
30 20
15 M, FU, n= 102, 70 Number Analyzed 102 participants 70 participants
23 18
18 M, FU, n= 96 ,65 Number Analyzed 96 participants 65 participants
23 18
21 M, FU, n= 92, 59 Number Analyzed 92 participants 59 participants
22 16
24 M, FU, n= 80, 53 Number Analyzed 80 participants 53 participants
20 15
27 M, FU, n= 74, 44 Number Analyzed 74 participants 44 participants
15 13
30 M, FU, n= 69, 35 Number Analyzed 69 participants 35 participants
14 8
33 M, FU, n= 65, 29 Number Analyzed 65 participants 29 participants
15 7
36 M, FU, n= 58, 23 Number Analyzed 58 participants 23 participants
12 7
39 M, FU, n= 51, 18 Number Analyzed 51 participants 18 participants
12 7
42 M, FU, n= 44, 16 Number Analyzed 44 participants 16 participants
11 6
45 M, FU, n= 39, 14 Number Analyzed 39 participants 14 participants
8 4
48 M, FU, n= 37, 12 Number Analyzed 37 participants 12 participants
8 2
51 M, FU, n= 32, 12 Number Analyzed 32 participants 12 participants
7 3
54 M, FU, n= 30, 9 Number Analyzed 30 participants 9 participants
7 2
57 M, FU, n= 26, 9 Number Analyzed 26 participants 9 participants
3 3
60 M, FU, n= 26, 8 Number Analyzed 26 participants 8 participants
3 3
8.Secondary Outcome
Title Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time
Hide Description Participants with no B-symptoms (B-Sy) (no night sweat, no weight loss, no fever and no extreme fatigue) and at least one indicated B-sy(night sweats, weight loss, fever or extreme fatigue) were presented at Screening, Cycle 1 Day 1, Cycle 2 Day1, Cycle 3 Day1, Cycle 4 Day1, Cycle 5 Day1, Cycle 6 Day 1 and during follow up period at 1 M after study drug therapy, then every 3 M up to 5 year (up to 60 months).
Time Frame Screening, Cycle1 Day 1, Cycle 2 Day1, Cycle 3 Day1, Cycle 4 Day1, Cycle 5 Day1, Cycle 6 Day 1 and During at 1M after study drug therapy, 3M, then every 3 M up to 5 year (up to 60 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Arm/Group Title Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Fludarabine + Cyclophosphamide_ ITT Subjects
Hide Arm/Group Description:
Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared [m^2] and cyclophosphamide was administered at 250mg/m^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m^2 and cyclophosphamide administered at 250mg/m^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Overall Number of Participants Analyzed 183 182
Measure Type: Number
Unit of Measure: Participants
Screening, no B-sy, n= 183, 180 Number Analyzed 183 participants 180 participants
63 59
Screening, one B-sy, n= 183, 180 Number Analyzed 183 participants 180 participants
120 121
Cycle 1 Day 1, no B-sy, n= 179, 179 Number Analyzed 179 participants 179 participants
64 68
Cycle 1 Day 1, one B-sy, n= 179, 179 Number Analyzed 179 participants 179 participants
115 111
Cycle 2 Day 1,no B-sy, n= 168, 170 Number Analyzed 168 participants 170 participants
116 108
Cycle 2 Day 1, one B-sy, n= 168, 170 Number Analyzed 168 participants 170 participants
52 62
Cycle 3 Day 1, no B-sy, n= 165, 156 Number Analyzed 165 participants 156 participants
131 116
Cycle 3 Day 1, one B-sy, n= 165, 156 Number Analyzed 165 participants 156 participants
34 40
Cycle 4 Day 1, no B-sy, n= 154, 132 Number Analyzed 154 participants 132 participants
129 107
Cycle 4 Day 1, one B-sy, n= 154, 132 Number Analyzed 154 participants 132 participants
25 25
Cycle 5 Day 1, no B-sy, n= 134, 118 Number Analyzed 134 participants 118 participants
120 97
Cycle 5 Day 1, one B-sy, n= 134, 118 Number Analyzed 134 participants 118 participants
14 21
Cycle 6 Day 1, no B-sy, n= 120, 95 Number Analyzed 120 participants 95 participants
111 82
Cycle 6 Day 1, one B-sy, n= 120, 95 Number Analyzed 120 participants 95 participants
9 13
1 M, FU, no B-sy, n= 161, 145 Number Analyzed 161 participants 145 participants
141 116
1 M, FU, one B-sy, n= 161, 145 Number Analyzed 161 participants 145 participants
20 29
3 M, FU, no B-sy, n= 153, 119 Number Analyzed 153 participants 119 participants
136 105
3 M, FU, one B-sy, n= 153, 119 Number Analyzed 153 participants 119 participants
17 14
6 M, FU, no B-sy, n= 138, 107 Number Analyzed 138 participants 107 participants
123 96
6 M, FU, one B-sy, n= 138, 107 Number Analyzed 138 participants 107 participants
15 11
9 M, FU, no B-sy, n= 129, 96 Number Analyzed 129 participants 96 participants
116 87
9 M, FU, one B-sy, n= 129, 96 Number Analyzed 129 participants 96 participants
13 9
12 M, FU, no B-sy, n= 119, 87 Number Analyzed 119 participants 87 participants
108 74
12 M, FU, one B-sy, n= 119, 87 Number Analyzed 119 participants 87 participants
11 13
15 M, FU, no B-sy, n= 103, 71 Number Analyzed 103 participants 71 participants
98 63
15 M, FU, one B-sy, n= 103, 71 Number Analyzed 103 participants 71 participants
5 8
18 M, FU, no B-sy, n= 98, 64 Number Analyzed 98 participants 64 participants
93 58
18 M, FU, one B-sy, n= 98, 64 Number Analyzed 98 participants 64 participants
5 6
21 M, FU, no B-sy, n= 94, 60 Number Analyzed 94 participants 60 participants
87 55
21 M, FU, one B-sy , n= 94, 60 Number Analyzed 94 participants 60 participants
7 5
24 M, FU, no B-sy, n= 80, 52 Number Analyzed 80 participants 52 participants
79 48
24 M, FU, one B-sy, n= 80, 52 Number Analyzed 80 participants 52 participants
1 4
27 M, FU, no B-sy, n= 74, 45 Number Analyzed 74 participants 45 participants
71 41
27 M, FU, one B-syn, n= 74, 45 Number Analyzed 74 participants 45 participants
4 3
30 M, FU, no B-sy, n= 70, 35 Number Analyzed 70 participants 35 participants
68 33
30 M, FU, one B-sy, n= 70, 35 Number Analyzed 70 participants 35 participants
2 2
33 M, FU, no B-sy, n= 66, 29 Number Analyzed 66 participants 29 participants
63 27
33 M, FU, one B-sy, n= 66, 29 Number Analyzed 66 participants 29 participants
3 2
36 M, FU, no B-sy, n=58, 23 Number Analyzed 58 participants 23 participants
56 23
36 M, FU, one B-sy, n=58, 23 Number Analyzed 58 participants 23 participants
2 0
39 M, FU, no B-sy, n=52, 18 Number Analyzed 52 participants 18 participants
49 18
39 M, FU, one B-sy, n=52, 18 Number Analyzed 52 participants 18 participants
3 0
42 M, FU, no B-sy, n=45, 16 Number Analyzed 45 participants 16 participants
45 16
42 M, FU, one B-sy, n=45, 16 Number Analyzed 45 participants 16 participants
0 0
45 M, FU, no B-sy, n=n=41, 15 Number Analyzed 41 participants 15 participants
41 14
45 M, FU, one B-sy, n=41, 15 Number Analyzed 41 participants 15 participants
0 1
48 M, FU, no B-sy, n=37, 13 Number Analyzed 37 participants 13 participants
36 13
48 M, FU, one B-sy, n=37, 13 Number Analyzed 37 participants 13 participants
1 0
51 M, FU, no B-sy, n=32, 12 Number Analyzed 32 participants 12 participants
32 11
51 M, FU, one B-sy, n=32, 12 Number Analyzed 32 participants 12 participants
0 1
54 M, FU, no B-sy, n=30, 10 Number Analyzed 30 participants 10 participants
30 10
54 M, FU, one B-sy, n=30, 10 Number Analyzed 30 participants 10 participants
0 0
57 M, FU, no B-sy, n=26, 9 Number Analyzed 26 participants 9 participants
26 9
57 M, FU, one B-sy, n=26, 9 Number Analyzed 26 participants 9 participants
0 0
60 M, FU, no B-sy, n=25, 9 Number Analyzed 25 participants 9 participants
24 9
60 M, FU, one B-sy, n=25, 9 Number Analyzed 25 participants 9 participants
1 0
9.Secondary Outcome
Title Percentage of Participants With the Best Overall Response (OR), as Assessed by the IRC
Hide Description OR is defined as the number of participants achieving an objective response (complete response [CR], CR with incomplete bone marrow recovery [CRi], partial response [PR], and nodular PR [nPR]). CR (all the criteria at least 2 months after last treatment): no lymphadenopathy (Ly) > 1.5 cm/ hepatomegaly/ splenomegaly/ constitutional symptoms; neutrophils >1500 per microliter (µL), platelets (PL) >100,000/µL, hemoglobin (Hb) >11 grams/deciliter (g/dL), lymphocytes (LC) <4000/µL, bone marrow (BM) sample must be normocellular for age, <30% LC, no lymphoid nodule. CRi: CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. PR: >=50% decrease in LC, Ly, size of liver and spleen and at least one of the following results: PL >100,000/µL or 50% improvement over Baseline (BL), Hb >11 g/dL or 50% improvement over BL. nPR: persistent nodules BM.
Time Frame From randomization up to 5 years after last dose of study drug
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ITT Population
Arm/Group Title Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Fludarabine + Cyclophosphamide_ ITT Subjects
Hide Arm/Group Description:
Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared [m^2] and cyclophosphamide was administered at 250mg/m^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m^2 and cyclophosphamide administered at 250mg/m^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Overall Number of Participants Analyzed 183 182
Measure Type: Number
Unit of Measure: Percentage of participants
CR 27 7
CRi 2 1
nPR 0 0
PR 55 59
Stable disease 11 28
Progressive Disease 0 0
Not Evaluable 4 2
Missing 1 2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects, Fludarabine + Cyclophosphamide_ ITT Subjects
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
10.Secondary Outcome
Title Percentage of Participants With the Best OR, as Assessed by the Investigator
Hide Description

OR is defined as the number of participants achieving an objective response (complete response [CR], CR with incomplete bone marrow recovery [CRi], partial response [PR], and nodular PR [nPR]). CR (all the criteria at least 2 months after last treatment): no lymphadenopathy (Ly) > 1.5 cm/ hepatomegaly/ splenomegaly/ constitutional symptoms; neutrophils >1500 per microliter (µL), platelets (PL) >100,000/µL, hemoglobin (Hb) >11 grams/deciliter (g/dL), lymphocytes (LC) <4000/µL, bone marrow (BM) sample must be normocellular for age, <30% LC, no lymphoid nodule. CRi: CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. PR: >=50% decrease in LC, Ly, size of liver and spleen and at least one of the following results: PL >100,000/µL or 50% improvement over Baseline (BL), Hb >11 g/dL or 50% improvement over BL. nPR: persistent nodules BM.

Responder = CR + CRi + NPR + PR

Time Frame From randomization up to 5 years after last dose of study drug
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ITT Population
Arm/Group Title Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Fludarabine + Cyclophosphamide_ ITT Subjects
Hide Arm/Group Description:
Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared [m^2] and cyclophosphamide was administered at 250mg/m^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m^2 and cyclophosphamide administered at 250mg/m^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Overall Number of Participants Analyzed 183 182
Measure Type: Number
Unit of Measure: Percentage of participants
CR 45 24
CRi 12 4
nPR 2 8
PR 107 113
Stable disease 9 21
Progressive Disease 0 3
Missing 8 9
Responder 166 149
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects, Fludarabine + Cyclophosphamide_ ITT Subjects
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0166
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
11.Secondary Outcome
Title Number of Participants Who Were Negative for Minimal Residual Disease (MRD) Assessed by IRC
Hide Description MRD refers to small number of leukemic cells that remain in the participant during treatment or after treatment at the time the participant achieved a confirmed CR. MRD analysis was performed for the participants who were suspected of achieving a primary endpoint CR. MDR was performed by flow cytometry on a bone marrow or peripheral blood sample taken at least 2 months after final treatment. MRD negative was defined as less than one CLL cell per 10000 leukocytes.
Time Frame From randomization up to 5 years after last dose of study drug
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Arm/Group Title Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Fludarabine + Cyclophosphamide_ ITT Subjects
Hide Arm/Group Description:
Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared [m^2] and cyclophosphamide was administered at 250mg/m^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m^2 and cyclophosphamide administered at 250mg/m^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Overall Number of Participants Analyzed 183 182
Measure Type: Number
Unit of Measure: Participants
Screening, n= 46, 13 Number Analyzed 46 participants 13 participants
0 0
Cycle 1 Day 1, n= 2, 0 Number Analyzed 2 participants 0 participants
0
3 M, FU, n= 44, 12 Number Analyzed 44 participants 12 participants
21 7
6 M, FU, n= 35, 11 Number Analyzed 35 participants 11 participants
25 6
9 M, FU, n= 29, 8 Number Analyzed 29 participants 8 participants
20 4
12 M, FU, n= 25, 4 Number Analyzed 25 participants 4 participants
16 1
15 M, FU, n= 20, 3 Number Analyzed 20 participants 3 participants
14 1
18 M, FU, n= 16, 2 Number Analyzed 16 participants 2 participants
12 1
21 M, FU, n= 13, 2 Number Analyzed 13 participants 2 participants
9 1
24 M, FU, n= 9, 2 Number Analyzed 9 participants 2 participants
8 1
27 M, FU, n= 9, 1 Number Analyzed 9 participants 1 participants
8 0
30 M, FU, n= 9, 2 Number Analyzed 9 participants 2 participants
8 2
33 M, FU, n= 5, 2 Number Analyzed 5 participants 2 participants
3 1
36 M, FU, n= 5, 2 Number Analyzed 5 participants 2 participants
5 1
39 M, FU, n= 2, 1 Number Analyzed 2 participants 1 participants
2 1
42 M, FU, n= 2, 0 Number Analyzed 2 participants 0 participants
2
45 M, FU, n= 1, 1 Number Analyzed 1 participants 1 participants
1 1
48 M, FU, n= 2, 1 Number Analyzed 2 participants 1 participants
2 1
51 M, FU, n= 2, 1 Number Analyzed 2 participants 1 participants
2 1
54 M, FU, n= 2, 1 Number Analyzed 2 participants 1 participants
2 1
12.Secondary Outcome
Title Number of Participants Who Were Negative for MRD Assessed by Investigator
Hide Description MRD refers to small number of leukemic cells that remain in the participant during treatment or after treatment at the time the participant achieved a confirmed CR. MRD analysis was performed for the participants who were suspected of achieving a primary endpoint CR. MDR was performed by flow cytometry on a bone marrow or peripheral blood sample taken at least 2 months after final treatment. MRD negative was defined as less than one CLL cell per 10000 leukocytes.
Time Frame From randomization up to 5 years after last dose of study drug
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Arm/Group Title Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Fludarabine + Cyclophosphamide_ ITT Subjects
Hide Arm/Group Description:
Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared [m^2] and cyclophosphamide was administered at 250mg/m^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m^2 and cyclophosphamide administered at 250mg/m^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Overall Number of Participants Analyzed 183 182
Measure Type: Number
Unit of Measure: Participants
Screening, n= 177, 171 Number Analyzed 177 participants 171 participants
0 1
3 M, FU, n= 120, 76 Number Analyzed 120 participants 76 participants
39 15
6 M, FU, n= 87, 57 Number Analyzed 87 participants 57 participants
48 11
9 M, FU, n= 71, 29 Number Analyzed 71 participants 29 participants
35 6
12 M, FU, n= 55, 18 Number Analyzed 55 participants 18 participants
31 3
15 M, FU, n= 38, 14 Number Analyzed 38 participants 14 participants
23 2
18 M, FU, n= 31, 13 Number Analyzed 31 participants 13 participants
20 2
21 M, FU, n= 27, 9 Number Analyzed 27 participants 9 participants
16 3
24 M, FU, n= 15, 4 Number Analyzed 15 participants 4 participants
13 2
27 M, FU, n= 18, 5 Number Analyzed 18 participants 5 participants
14 1
30 M, FU, n= 15, 3 Number Analyzed 15 participants 3 participants
12 3
33 M, FU, n= 13, 3 Number Analyzed 13 participants 3 participants
8 2
36 M, FU, n= 10, 4 Number Analyzed 10 participants 4 participants
9 2
39 M, FU, n= 7, 3 Number Analyzed 7 participants 3 participants
6 2
42 M, FU, n= 8, 1 Number Analyzed 8 participants 1 participants
7 1
45 M, FU, n= 7, 2 Number Analyzed 7 participants 2 participants
6 2
48 M, FU, n= 6, 3 Number Analyzed 6 participants 3 participants
6 2
51 M, FU, n= 6, 2 Number Analyzed 6 participants 2 participants
5 1
54 M, FU, n= 7, 2 Number Analyzed 7 participants 2 participants
4 2
57 M, FU, n= 4, 3 Number Analyzed 4 participants 3 participants
3 2
60 M, FU, n= 3, 3 Number Analyzed 3 participants 3 participants
3 2
13.Secondary Outcome
Title Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)
Hide Description An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury.
Time Frame From first dose of study medication to 60 Days after the last dose of study medication (for an AE), or up to 5 years after the last dose of study drug or until the time of the next anti-CLL therapy (for SAE)
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Safety Population: Participants who received at least one dose of a study drug.
Arm/Group Title Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Fludarabine + Cyclophosphamide_ ITT Subjects
Hide Arm/Group Description:
Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared [m^2] and cyclophosphamide was administered at 250mg/m^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m^2 and cyclophosphamide administered at 250mg/m^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Overall Number of Participants Analyzed 181 178
Measure Type: Number
Unit of Measure: Participants
AE 170 153
SAE 108 86
14.Secondary Outcome
Title Number of Participants With a Human Anti-human Antibody (HAHA) Positive Result at Indicated Time Points
Hide Description Serum samples for analysis of HAHA were collected at Baseline (Screening), after 3 cycles were compelted, after 1 M and 6 M post last dose. All samples were first tested in a screening step; positive samples from the screening were further evaluated in a confirmation test. The confirmed positive samples were reported as HAHA-positive.
Time Frame From start of study drug until 60 days after the last dose of study medication
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles)
Arm/Group Title Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Fludarabine + Cyclophosphamide_ ITT Subjects
Hide Arm/Group Description:
Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared [m^2] and cyclophosphamide was administered at 250mg/m^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m^2 and cyclophosphamide administered at 250mg/m^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Overall Number of Participants Analyzed 181 178
Measure Type: Number
Unit of Measure: Participants
Screening Visit, n= 179,177 Number Analyzed 179 participants 177 participants
8 1
Cycle 4 Day 1, n= 151,130 Number Analyzed 151 participants 130 participants
0 2
1 M, FU, n= 148,132 Number Analyzed 148 participants 132 participants
0 2
3 M, FU, n= 0,1 Number Analyzed 0 participants 1 participants
0
6 M, FU, n= 130, 99 Number Analyzed 130 participants 99 participants
2 0
9 M, FU, n= 0, 2 Number Analyzed 0 participants 2 participants
0
30 M, FU, n= 2, 0 Number Analyzed 2 participants 0 participants
0
15.Secondary Outcome
Title Number of Participants With Autoimmune Hemolytic Anaemia (AIHA)
Hide Description AIHA is a condition where the body's immune system fails to recognize red blood cells as "self" and begins destroying these red blood cells. The number of participants experienced AIHA are presented.
Time Frame From first dose of study medication to 60 days after the last dose of study medication (for an AE), or up to 5 years after the last dose of study drug or until the time of the next anti-CLL therapy (for SAE)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Fludarabine + Cyclophosphamide_ ITT Subjects
Hide Arm/Group Description:
Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared [m^2] and cyclophosphamide was administered at 250mg/m^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m^2 and cyclophosphamide administered at 250mg/m^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Overall Number of Participants Analyzed 181 178
Measure Type: Number
Unit of Measure: Participants
3 2
16.Secondary Outcome
Title Number of Participants With Drug Related Infections Reported as AEs and SAEs of Maximum Severity of Grade 3 or Higher
Hide Description An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Maximum severity grades were evaluated according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 3.0 (1, mild; 2, moderate; 3, severe; 4, life-threatening/disabling; 5, death).
Time Frame From first dose of study medication to 60 days after the last dose of study medication (for an AE), or up to 5 years after the last dose of study drug or until the time of the next anti-CLL therapy (for SAE)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Fludarabine + Cyclophosphamide_ ITT Subjects
Hide Arm/Group Description:
Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared [m^2] and cyclophosphamide was administered at 250mg/m^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m^2 and cyclophosphamide administered at 250mg/m^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Overall Number of Participants Analyzed 181 178
Measure Type: Number
Unit of Measure: Participants
AE 19 11
SAE 25 21
17.Secondary Outcome
Title Number of Participants With at Least One Grade 3/Grade 4 Myelosuppression Adverse Events
Hide Description Participants with at least one Grade 3 or Grade 4 myelosuppression (anemia, neutropenia, and thrombocytopenia) are presented. Myelosuppression is defined as the decrease in the ability of the bone marrow to produce blood cells. AEs were graded according to NCI common terminology criteria for adverse events (CTCAE) grade, version 3.0 (1, mild; 2, moderate; 3, severe; 4, life-threatening/disabling; 5, death).
Time Frame From first dose of study medication to 60 days after the last dose of study medication (for an AE), or up to 5 years after the last dose of study drug or until the time of the next anti-CLL therapy (for SAE)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Fludarabine + Cyclophosphamide_ ITT Subjects
Hide Arm/Group Description:
Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared [m^2] and cyclophosphamide was administered at 250mg/m^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m^2 and cyclophosphamide administered at 250mg/m^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Overall Number of Participants Analyzed 181 178
Measure Type: Number
Unit of Measure: Participants
126 118
18.Secondary Outcome
Title Number of Participants Who Received no Transfusion or at Least One Transfusion During the Study
Hide Description Participants who received no transfusion and at least one transfusion during the study are presented. Participants who took any blood products or blood supportive care product are included.
Time Frame From randomization up to 5 years after last dose of study drug
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Fludarabine + Cyclophosphamide_ ITT Subjects
Hide Arm/Group Description:
Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared [m^2] and cyclophosphamide was administered at 250mg/m^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m^2 and cyclophosphamide administered at 250mg/m^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Overall Number of Participants Analyzed 181 178
Measure Type: Number
Unit of Measure: Participants
At least one transfusion 125 99
No transfusions 56 79
19.Secondary Outcome
Title Mean Level of Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM
Hide Description Immunoglobulins, or antibodies, are large proteins used by the immune system to identify and neutralize foreign particles such as bacteria and viruses. Their normal blood levels indicate proper immune status. Low levels indicate immuno-suppression. Blood samples were collected from each participant and IgA, IgG, and IgM were measured at Baseline, and 1M and 6M after last dose during follow up period.
Time Frame Baseline, 1M and 6M follow up
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Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Arm/Group Title Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Fludarabine + Cyclophosphamide_ ITT Subjects
Hide Arm/Group Description:
Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared [m^2] and cyclophosphamide was administered at 250mg/m^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m^2 and cyclophosphamide administered at 250mg/m^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Overall Number of Participants Analyzed 181 178
Mean (Standard Deviation)
Unit of Measure: Gram per liter
Cycle 1 Day 1, IgA, n= 179, 175 Number Analyzed 179 participants 175 participants
1.0  (0.74) 0.9  (0.68)
Cycle 1 Day 1, IgG, n= 179, 175 Number Analyzed 179 participants 175 participants
8.7  (5.22) 8.2  (3.86)
Cycle 1 Day 1, IgM, n= 179, 175 Number Analyzed 179 participants 175 participants
0.6  (1.36) 0.8  (1.77)
1 M, FU, IgA, n= 150, 131 Number Analyzed 150 participants 131 participants
1.0  (0.79) 1.0  (0.77)
1 M, FU, IgG, n= 150, 131 Number Analyzed 150 participants 131 participants
7.9  (4.05) 7.9  (3.38)
1 M, FU, IgM, n= 150, 131 Number Analyzed 150 participants 131 participants
0.5  (1.16) 0.8  (1.88)
6 M, FU, IgA, n= 130, 101 Number Analyzed 130 participants 101 participants
1.0  (0.77) 1.0  (0.76)
6 M, FU, IgG, n= 130, 101 Number Analyzed 130 participants 101 participants
7.8  (3.97) 8.9  (4.31)
6 M, FU, IgM, n= 130, 101 Number Analyzed 130 participants 101 participants
0.4  (0.50) 1.1  (1.98)
9 M, FU, IgA, n= 1, 2 Number Analyzed 1 participants 2 participants
0.9 [1]   (NA) 0.9  (0.21)
9 M, FU, IgG, n= 1, 2 Number Analyzed 1 participants 2 participants
15.2 [1]   (NA) 8.8  (6.87)
9 M, FU, IgM, n= 1, 2 Number Analyzed 1 participants 2 participants
0.8 [1]   (NA) 0.2  (0.04)
18 M, FU, IgA, n= 0, 1 Number Analyzed 0 participants 1 participants
2.4 [1]   (NA)
18 M, FU, IgG, n= 0, 1 Number Analyzed 0 participants 1 participants
9.1 [1]   (NA)
18 M, FU, IgM, n= 0, 1 Number Analyzed 0 participants 1 participants
1.0 [1]   (NA)
30 M, FU, IgA, n= 2, 0 Number Analyzed 2 participants 0 participants
1.3  (1.17)
30 M, FU, IgG, n= 2, 0 Number Analyzed 2 participants 0 participants
4.7  (0.33)
30 M, FU, IgM, n= 2, 0 Number Analyzed 2 participants 0 participants
0.4  (0.26)
[1]
No standard deviation was able to be calculated for this data point because only one participant was analyzed.
20.Secondary Outcome
Title Change From Baseline in Cluster of Differentiation (CD) Cell Counts, CD5+ and CD19+
Hide Description CD5+ and CD19+ cells were counted by flow cytometry at Screening (Baseline) on Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 during the treatment period and after last dose of study drug at 1 M and then every three month follow up up to 45 M. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus. Baseline is defined as the assessment closest to but prior to first dose (e.g. day 1 if available, otherwise, screening). Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame Screening, Cycle 1 Day1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 and after last dose at 1 M and then every three months up to 45 M during Follow-up Period
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Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Arm/Group Title Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Fludarabine + Cyclophosphamide_ ITT Subjects
Hide Arm/Group Description:
Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared [m^2] and cyclophosphamide was administered at 250mg/m^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m^2 and cyclophosphamide administered at 250mg/m^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Overall Number of Participants Analyzed 183 182
Mean (Standard Deviation)
Unit of Measure: cells/uL
Cycle 1 Day 1,n=71, 65 Number Analyzed 71 participants 65 participants
43180.6  (48784.64) 53208.7  (70944.56)
Cycle 1 Day 15, n= 69, 62 Number Analyzed 69 participants 62 participants
2656.9  (6418.02) 9244.0  (19610.62)
Cycle 2 Day 1, n= 68, 63 Number Analyzed 68 participants 63 participants
2057.4  (5525.72) 10318.8  (21453.15)
Cycle 2 Day 15, n= 68, 59 Number Analyzed 68 participants 59 participants
513.7  (1717.65) 6874.4  (20632.64)
Cycle 3 Day 1,n= 68, 59 Number Analyzed 68 participants 59 participants
790.0  (2953.42) 6423.6  (19725.57)
Cycle 4 Day 1, n= 62, 49 Number Analyzed 62 participants 49 participants
402.1  (1768.74) 2643.2  (8092.22)
Cycle 5 Day 1,n= 57, 45 Number Analyzed 57 participants 45 participants
142.6  (472.24) 2838.6  (8314.08)
Cycle 6 Day 1, n= 56, 39 Number Analyzed 56 participants 39 participants
109.8  (398.77) 3862.7  (13312.14)
1 M, FU, n= 64, 61 Number Analyzed 64 participants 61 participants
163.5  (685.41) 5514.3  (17369.97)
3 M, FU, n= 69, 47 Number Analyzed 69 participants 47 participants
671.3  (2786.99) 2604.9  (9229.90)
6 M, FU, n= 61, 42 Number Analyzed 61 participants 42 participants
1591.6  (8857.22) 2275.6  (5118.00)
9 M, FU, n= 56, 37 Number Analyzed 56 participants 37 participants
910.5  (2495.85) 3408.4  (7438.45)
12 M, FU, n= 47, 30 Number Analyzed 47 participants 30 participants
2303.2  (6675.70) 2876.5  (6252.53)
15 M, FU, n= 35, 18 Number Analyzed 35 participants 18 participants
3325.8  (8006.48) 3072.7  (9038.23)
18 M, FU, n= 22, 12 Number Analyzed 22 participants 12 participants
1607.5  (2935.82) 4549.8  (8839.23)
21 M, FU, n= 22, 10 Number Analyzed 22 participants 10 participants
3830.8  (8989.02) 5236.9  (10537.31)
24 M, FU, n= 9, 6 Number Analyzed 9 participants 6 participants
1244.6  (1300.01) 7843.3  (11897.55)
27 M, FU, n= 7, 4 Number Analyzed 7 participants 4 participants
1877.4  (2117.84) 6128.0  (9161.38)
30 M, FU, n= 6, 2 Number Analyzed 6 participants 2 participants
5029.7  (8266.90) 6515.5  (5916.36)
33 M, FU, n= 4, 1 Number Analyzed 4 participants 1 participants
14166.8  (20166.09) 5208.0 [1]   (NA)
36 M, FU, n= 3, 1 Number Analyzed 3 participants 1 participants
1187.0  (1407.79) 8184.0 [1]   (NA)
39 M, FU, n=1, 0 Number Analyzed 1 participants 0 participants
557.0 [1]   (NA)
42 M, FU, n= 1, 0 Number Analyzed 1 participants 0 participants
1640.0 [1]   (NA)
45 M, FU, n= 2, 0 Number Analyzed 2 participants 0 participants
4689.0  (1493.41)
48 M FU, n= 1, 1 Number Analyzed 1 participants 1 participants
27755.0 [1]   (NA) 29155.0 [1]   (NA)
54 M FU, n= 1, 0 Number Analyzed 1 participants 0 participants
189849.0 [1]   (NA)
[1]
No standard deviation was able to be calculated for this data point because only one participant was analyzed.
21.Secondary Outcome
Title Change From Baseline in Cell Counts, CD5- CD19+
Hide Description CD5- CD19+ cells were counted by flow cytometry at Screening (baseline) at Cycle 1 Day1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 during treatment period and after last dose of study drug at 1 M and then every three month up to 45 M during follow up period. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus. Baseline is defined as the assessment closest to but prior to first dose (e.g. Day 1 if available otherwise screening). Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame Screening, Cycle 1 Day1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 and after last dose at 1 M and then every three month up to 45 M during Follow-up Period
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Safety Population
Arm/Group Title Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Fludarabine + Cyclophosphamide_ ITT Subjects
Hide Arm/Group Description:
Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared [m^2] and cyclophosphamide was administered at 250mg/m^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m^2 and cyclophosphamide administered at 250mg/m^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Overall Number of Participants Analyzed 181 178
Mean (Standard Deviation)
Unit of Measure: cells/uL
Screening, n= 71, 62 Number Analyzed 71 participants 62 participants
4817.8  (20948.17) 6959.1  (39980.14)
Cycle 1 Day 1,n= 71, 65 Number Analyzed 71 participants 65 participants
5996.7  (22331.29) 2041.3  (4418.63)
Cycle 1 Day 15, n= 69, 62 Number Analyzed 69 participants 62 participants
239.0  (1052.19) 351.7  (1377.56)
Cycle 2 Day 1, n= 68, 63 Number Analyzed 68 participants 63 participants
115.4  (403.09) 465.7  (1610.05)
Cycle 2 Day 15,n= 68, 59 Number Analyzed 68 participants 59 participants
35.6  (133.75) 331.3  (1177.18)
Cycle 3 Day 1,n= 68, 59 Number Analyzed 68 participants 59 participants
39.5  (144.64) 179.7  (520.63)
Cycle 4 Day 1, n= 62, 49 Number Analyzed 62 participants 49 participants
25.7  (92.88) 95.3  (369.19)
Cycle 5 Day 1, n= 57, 45 Number Analyzed 57 participants 45 participants
15.9  (77.11) 195.5  (945.34)
Cycle 6 Day 1, n= 56, 39 Number Analyzed 56 participants 39 participants
10.0  (29.85) 649.7  (3606.28)
1 M, FU, n= 64, 61 Number Analyzed 64 participants 61 participants
7.5  (19.54) 863.8  (5001.84)
3 M, FU, n= 69, 47 Number Analyzed 69 participants 47 participants
40.1  (238.18) 172.0  (681.28)
6 M, FU, n= 61, 42 Number Analyzed 61 participants 42 participants
21.2  (58.16) 50.7  (49.13)
9 M, FU, n= 56, 37 Number Analyzed 56 participants 37 participants
85.7  (359.01) 92.0  (101.16)
12 M, FU, n= 47, 30 Number Analyzed 47 participants 30 participants
89.9  (226.06) 220.1  (698.57)
15 M, FU, n= 35, 18 Number Analyzed 35 participants 18 participants
67.3  (59.52) 94.6  (70.17)
18 M, FU, n= 22, 12 Number Analyzed 22 participants 12 participants
126.1  (188.25) 92.3  (69.14)
21 M, FU, n= 22, 10 Number Analyzed 22 participants 10 participants
375.5  (1307.35) 108.3  (95.86)
24 M, FU, n= 9, 6 Number Analyzed 9 participants 6 participants
74.0  (57.46) 104.5  (70.46)
27 M, FU, n= 7, 4 Number Analyzed 7 participants 4 participants
73.9  (60.40) 187.5  (200.85)
30 M, FU, n= 6, 2 Number Analyzed 6 participants 2 participants
74.2  (58.82) 129.5  (5303)
33 M, FU, n= 4, 1 Number Analyzed 4 participants 1 participants
41.8  (40.13) 1003.0 [1]   (NA)
36 M, FU, n= 3, 1 Number Analyzed 3 participants 1 participants
107.3  (86.75) 1506.0 [1]   (NA)
39 M, FU, n= 1, 0 Number Analyzed 1 participants 0 participants
13.0 [1]   (NA)
42 M, FU, n= 1, 0 Number Analyzed 1 participants 0 participants
13.0 [1]   (NA)
45 M, FU, n= 2, 0 Number Analyzed 2 participants 0 participants
166.5  (222.74)
48 M, FU, n= 1,1 Number Analyzed 1 participants 1 participants
6528.0 [1]   (NA) 28.0 [1]   (NA)
54 M, FU, n= 1, 0 Number Analyzed 1 participants 0 participants
690.0 [1]   (NA)
[1]
No standard deviation was able to be calculated for this data point because only one participant was analyzed.
22.Secondary Outcome
Title Prognostic and Biological Markers Correlating With Clinical Response
Hide Description Blood samples were collected for the assessment of the following prognostic markers at BL: immunoglobulin heavy chain variable region(IgVH) homology; Zeta-Chain-Associated Protein Kinase 70(ZAP70), VH3-21 usage; Cytogenetics (by fluorescent in situ hybridization [FISH]); beta 2 microglobulin. Cox-regression model was used to explore the relationship between progression-free survival and the following explanatory variables: treatment group, cytogenetics (analyzed by FISH included 6q-,11q-, +12q, 17p-, 13q-) , ZAP-70 (positive, negative or intermediate), VH3-21 usage (Yes and No), IgVH homology (>98%, 97%-98% and <97%), beta 2 microglobulin (>3500 microgram per liter [µg/L] and <=3500 µg/L). For each covariate, a hazard ratio <1 indicates a lower risk on the first effect tested compared with the other effects tested. Cytogenetics Group (based on >=20%)=cytogenetics (CY G).
Time Frame From randomization up to 5 years after last dose of study drug
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ITT Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Fludarabine + Cyclophosphamide_ ITT Subjects
Hide Arm/Group Description:
Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared [m^2] and cyclophosphamide was administered at 250mg/m^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m^2 and cyclophosphamide administered at 250mg/m^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Overall Number of Participants Analyzed 183 182
Measure Type: Number
Unit of Measure: Participants
B2 Microglobulin G 1: > 3500 microgram/liter (μg/L Number Analyzed 183 participants 182 participants
79 78
B2 Microglobulin G 1: <= 3500 ug/L, n=51,47 Number Analyzed 51 participants 47 participants
22 26
CY G 1: 11q-, n=40, 31 Number Analyzed 40 participants 31 participants
29 19
CY G 1: 17p-, n=7, 13 Number Analyzed 7 participants 13 participants
6 9
CY G 1: 6q- or +12q or 13q-, n=84, 80 Number Analyzed 84 participants 80 participants
38 48
CY G 1: no aberration, n=45, 47 Number Analyzed 45 participants 47 participants
27 27
VH3-21 Usage Flag: Yes, n=9, 7 Number Analyzed 9 participants 7 participants
6 4
VH3-21 Usage Flag: No, n=159, 162 Number Analyzed 159 participants 162 participants
93 96
IgVH Homology, <97%, n=40, 43 Number Analyzed 40 participants 43 participants
13 15
IgVH Homology, 97%-98%, n=12, 10 Number Analyzed 12 participants 10 participants
5 7
IgVH Homology, >98%, n=115, 116 Number Analyzed 115 participants 116 participants
80 78
ZAP70 G 1, Negative, n=28, 32 Number Analyzed 28 participants 32 participants
14 13
ZAP70 G 1, Intermediate, n=54, 46 Number Analyzed 54 participants 46 participants
27 23
ZAP70, G1 Positive, n=94, 91 Number Analyzed 94 participants 91 participants
60 65
23.Secondary Outcome
Title Changes in Patient Reported Outcome (PRO) Measures and Scores for European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Chronic Lymphocytic Leukaemia 16 Item Module (EORTC QLQ-CLL 16)
Hide Description The EORTC QLQ-CLL16 is comprised of 16 questions that address 5 domains of health-related quality of life (HRQoL) important in CLL. There are 4 multi-item scales – fatigue (2 items), treatment side effects ([TSE], 4 items), disease symptoms (disease effects scale [DES], 4 items), and infection scale [IS] (4 items) – and single item scales (social activities [Social Problems (SP) Scale] and future health worries[Future Health (FH) Scale].). These are measured on a four point scale where 1 = not at all and 4 = very much. These scores are transformed to give a rating from 0 – 100, where 0 =no symptoms or problems and 100 = a severe symptoms or problems. EORTC QLQ-CLL16 was assessed at Screening; Cycle 4 Day 1 and during follow-up 1 M and every 3 M up to 24 months. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value was obtained at randomization.
Time Frame Screening, Cycle 3 Day 1, and 1 M and every 3 month post last dose up to 24 month.
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Participants
Arm/Group Title Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Fludarabine + Cyclophosphamide_ ITT Subjects
Hide Arm/Group Description:
Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared [m^2] and cyclophosphamide was administered at 250mg/m^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m^2 and cyclophosphamide administered at 250mg/m^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Overall Number of Participants Analyzed 183 182
Mean (Standard Deviation)
Unit of Measure: scores on a scale
DES, Cycle 4 Day 1, n=142,125 Number Analyzed 142 participants 125 participants
-8.5  (18.08) -9.0  (17.16)
DES, 1 M, FU, n=138, 123 Number Analyzed 138 participants 123 participants
-9.7  (19.18) -9.8  (19.89)
DES, 3 M, FU, n=145, 109 Number Analyzed 145 participants 109 participants
-8.2  (19.48) -10.9  (19.07)
DES, 6 M, FU, n= 126, 99 Number Analyzed 126 participants 99 participants
-9.8  (17.99) -11.6  (18.05)
DES, 9 M, FU, n=115, 85 Number Analyzed 115 participants 85 participants
-8.2  (20.70) -12.0  (17.04)
DES. 12 M, FU, n=109, 76 Number Analyzed 109 participants 76 participants
-10.1  (18.64) -10.2  (16.09)
DES, 15 M, FU, n=98, 62 Number Analyzed 98 participants 62 participants
-8.6  (18.08) -10.2  (16.91)
DES, 18 M, FU, n=90, 59 Number Analyzed 90 participants 59 participants
-8.5  (18.53) -11.6  (18.79)
DES, 21 M, FU, n=87, 53 Number Analyzed 87 participants 53 participants
-8.2  (18.48) -11.3  (17.60)
DES, 24 M, FU, n=70, 50 Number Analyzed 70 participants 50 participants
-7.1  (19.93) -13.6  (16.18)
Fatigue Scale (FS), Cycle 4 Day 1, n=142, 125 Number Analyzed 142 participants 125 participants
-7.0  (22.57) -7.1  (24.16)
FS, 1 M, FU, n=139, 123 Number Analyzed 139 participants 123 participants
-5.4  (29.16) -6.2  (28.74)
FS, 3 M, FU, n=144, 109 Number Analyzed 144 participants 109 participants
-4.4  (26.30) -8.3  (30.14)
FS, 6 M, FU, n=126, 99 Number Analyzed 126 participants 99 participants
-7.1  (25.94) -12.0  (25.98)
FS, 9 M, FU, n= 115, 85 Number Analyzed 115 participants 85 participants
-6.2  (27.08) -10.6  (26.95)
FS. 12 M, FU, n=109, 76 Number Analyzed 109 participants 76 participants
-7.3  (27.26) -8.1  (25.75)
FS, 15 M, FU, n=97, 62 Number Analyzed 97 participants 62 participants
-7.6  (22.57) -9.9  (24.04)
FS, 18 M, FU, n=90,59 Number Analyzed 90 participants 59 participants
-7.0  (23.03) -3.7  (33.34)
FS, 21 M, FU, n=87, 53 Number Analyzed 87 participants 53 participants
-10.3  (24.28) -8.2  (27.27)
FS, 24 M, FU, n=69, 50 Number Analyzed 69 participants 50 participants
-8.7  (24.19) -8.7  (25.48)
FH, Cycle 4 Day 1, n=141, 123 Number Analyzed 141 participants 123 participants
-11.8  (32.89) -10.6  (27.76)
FH, 1 M, FU, n=139, 120 Number Analyzed 139 participants 120 participants
-15.3  (35.04) -11.9  (29.56)
FH, 3 M, FU, n=145, 107 Number Analyzed 145 participants 107 participants
-14.3  (33.96) -14.0  (32.06)
FH, 6 M, FU, n=126, 96 Number Analyzed 126 participants 96 participants
-13.4  (33.98) -17.7  (30.57)
FH, 9 M, FU, n=113, 81 Number Analyzed 113 participants 81 participants
-15.6  (33.65) -13.2  (34.43)
FH. 12 M, FU, n=109, 74 Number Analyzed 109 participants 74 participants
-14.1  (32.80) -14.9  (33.63)
FH, 15 M, FU, n=98, 61 Number Analyzed 98 participants 61 participants
-14.6  (29.14) -14.2  (34.13)
FH, 18 M, FU, n=90, 58 Number Analyzed 90 participants 58 participants
-15.9  (31.69) -18.4  (33.72)
FH, 21 M, FU, n=87, 52 Number Analyzed 87 participants 52 participants
-16.9  (28.70) -15.4  (29.12)
FH, 24 M, FU, n=70, 49 Number Analyzed 70 participants 49 participants
-21.0  (29.58) -17.7  (30.51)
IS, Cycle 4 Day 1, n=142,125 Number Analyzed 142 participants 125 participants
0.5  (17.65) -1.4  (18.23)
IS, 1 M, FU, n=138, 122 Number Analyzed 138 participants 122 participants
2.9  (22.79) 2.7  (24.06)
IS, 3 M, FU, n=144, 109 Number Analyzed 144 participants 109 participants
0.8  (19.42) 0.8  (20.99)
IS, 6 M, FU, n=126, 99 Number Analyzed 126 participants 99 participants
-1.2  (18.46) -0.9  (20.40)
IS, 9 M, FU, n=115, 85 Number Analyzed 115 participants 85 participants
-1.4  (18.81) 1.4  (22.45)
IS. 12 M, FU, n=109, 76 Number Analyzed 109 participants 76 participants
0.4  (19.22) 2.1  (20.92)
IS, 15 M, FU, n=97, 60 Number Analyzed 97 participants 60 participants
0.5  (17.56) 0.3  (18.79)
IS, 18 M, FU, n=89, 59 Number Analyzed 89 participants 59 participants
-2.0  (16.04) 0.9  (19.04)
IS, 21 M, FU, n=87, 53 Number Analyzed 87 participants 53 participants
-2.5  (18.13) 2.5  (22.09)
IS, 24 M, FU, n=69, 49 Number Analyzed 69 participants 49 participants
-0.5  (18.85) 0.5  (21.34)
SP Scale Cycle 4 Day 1, n=141, 125 Number Analyzed 141 participants 125 participants
1.9  (25.44) 0.3  (26.94)
SP Scale, 1 M, FU, n=137, 121 Number Analyzed 137 participants 121 participants
3.2  (34.51) 0.0  (35.22)
SP Scale, 3 M, FU, n=143, 109 Number Analyzed 143 participants 109 participants
-1.9  (33.04) -4.3  (35.75)
SP Scale, 6 M, FU, n=124, 98 Number Analyzed 124 participants 98 participants
-5.6  (31.73) -10.9  (30.56)
SP Scale, 9 M, FU, n=114, 85 Number Analyzed 114 participants 85 participants
-5.0  (30.15) -11.0  (31.45)
SP Scale. 12 M, FU, n=107, 75 Number Analyzed 107 participants 75 participants
-7.2  (31.06) -7.6  (34.47)
SP Scale, 15 M, FU, n=95, 61 Number Analyzed 95 participants 61 participants
-6.7  (30.21) -13.7  (30.05)
SP Scale, 18 M, FU, n=89, 59 Number Analyzed 89 participants 59 participants
-7.1  (31.57) -8.5  (40.40)
SP Scale, 21 M, FU, n=86, 53 Number Analyzed 86 participants 53 participants
-8.1  (31.07) -7.5  (37.92)
SP Scale, 24 M, FU, n=68, 50 Number Analyzed 68 participants 50 participants
-11.8  (24.27) -8.7  (36.15)
TSE, Cycle 4 Day 1, n=142, 125 Number Analyzed 142 participants 125 participants
-4.7  (16.15) -4.0  (16.78)
TSE, 1 M, FU, n=139, 123 Number Analyzed 139 participants 123 participants
-5.0  (18.09) -3.2  (19.08)
TSE, 3 M, FU, n=145,109 Number Analyzed 145 participants 109 participants
-3.7  (19.41) -4.3  (17.03)
TSE, 6 M, FU, n=126, 99 Number Analyzed 126 participants 99 participants
-6.0  (15.25) -4.8  (16.96)
TSE, 9 M, FU, n=115, 85 Number Analyzed 115 participants 85 participants
-4.3  (17.22) -5.1  (16.38)
TSE. 12 M, FU, n=109, 76 Number Analyzed 109 participants 76 participants
-5.2  (16.44) -3.2  (13.94)
TSE, 15 M, FU, n=98, 62 Number Analyzed 98 participants 62 participants
-4.0  (14.92) -4.2  (13.73)
TSE, 18 M, FU, n=90, 60 Number Analyzed 90 participants 60 participants
-4.4  (17.10) -3.6  (19.18)
TSE, 21 M, FU, n=87, 54 Number Analyzed 87 participants 54 participants
-4.7  (16.63) -4.0  (15.91)
TSE, 24 M, FU, n=70, 50 Number Analyzed 70 participants 50 participants
-5.4  (17.52) -6.5  (14.12)
24.Secondary Outcome
Title Change From Baseline in Patient Reported Outcome (PRO) as Assessed by EuroQoL Five-Dimension (EQ-5D) Score at Indicated Visit
Hide Description EQ-5D is comprised of a 5-item health status measure and a visual analogue scale (VAS) and is used to generate two scores: the utility score and the thermometer score. The utility score measures mobility, self-care, usual activities, pain, discomfort, and anxiety/depression. Responses to each of the 5 health states are measured on a 3-point scale (level 1 = no problem; level 2 = some or moderate problem(s) and level 3 = unable, or extreme problems). Responses are typically converted into health utilities or valuations on a scale ranging from 0 (death) to 1 (perfect health). The thermometer score ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. A Negative health status describes health state worse than death.Baseline is the most recent, non-missing value prior to or on the first study drug dose date.
Time Frame Screening, Cycle 3 Day 1, and 1 M and every 3 month post last dose up to 24 month.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Fludarabine + Cyclophosphamide_ ITT Subjects
Hide Arm/Group Description:
Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared [m^2] and cyclophosphamide was administered at 250mg/m^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m^2 and cyclophosphamide administered at 250mg/m^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Overall Number of Participants Analyzed 183 182
Mean (Standard Deviation)
Unit of Measure: Score on a scale
UT, Cycle 4 Day 1, n=136, 121 Number Analyzed 136 participants 121 participants
0.0  (0.27) 0.0  (0.21)
UT, 1 M, FU, n=133, 117 Number Analyzed 133 participants 117 participants
0.1  (0.22) 0.0  (0.28)
UT, 3 M, FU, n=141, 102 Number Analyzed 141 participants 102 participants
0.0  (0.27) 0.1  (0.23)
UT, 6 M, FU, n=122, 96 Number Analyzed 122 participants 96 participants
0.1  (0.24) 0.1  (0.24)
UT, 9 M, FU, n=110, 81 Number Analyzed 110 participants 81 participants
0.1  (0.26) 0.1  (0.24)
UT. 12 M, FU, n=107, 71 Number Analyzed 107 participants 71 participants
0.1  (0.21) 0.1  (0.22)
UT, 15 M, FU, n=96, 58 Number Analyzed 96 participants 58 participants
0.0  (0.23) 0.1  (0.24)
UT, 18 M, FU, n=88, 57 Number Analyzed 88 participants 57 participants
0.1  (0.21) 0.0  (0.34)
UT, 21 M, FU, n= 87, 52 Number Analyzed 87 participants 52 participants
0.1  (0.21) 0.1  (0.26)
UT, 24 M, FU, n=68, 47 Number Analyzed 68 participants 47 participants
0.1  (0.19) 0.1  (0.28)
VAS Cycle 4 Day 1, n=137, 122 Number Analyzed 137 participants 122 participants
6.1  (17.68) 5.6  (17.64)
VAS, 1 M, FU, n=138, 122 Number Analyzed 138 participants 122 participants
5.6  (20.73) 5.9  (22.83)
VAS, 3 M, FU, n=141, 107 Number Analyzed 141 participants 107 participants
5.7  (19.92) 9.6  (20.88)
VAS, 6 M, FU, n=124, 99 Number Analyzed 124 participants 99 participants
8.2  (18.84) 11.1  (19.08)
VAS, 9 M, FU, n=114, 85 Number Analyzed 114 participants 85 participants
8.1  (18.33) 11.9  (20.59)
VAS. 12 M, FU, n=108, 75 Number Analyzed 108 participants 75 participants
7.0  (21.93) 10.3  (21.21)
VAS, 15 M, FU, n=95, 62 Number Analyzed 95 participants 62 participants
8.0  (17.52) 13.1  (21.06)
VAS, 18 M, FU, n=89, 60 Number Analyzed 89 participants 60 participants
9.4  (17.86) 11.1  (25.40)
VAS, 21 M, FU, n=87, 53 Number Analyzed 87 participants 53 participants
8.1  (16.42) 11.3  (24.16)
VAS, 24 M, FU, n=69, 50 Number Analyzed 69 participants 50 participants
8.8  (19.50) 15.2  (21.88)
25.Secondary Outcome
Title Change From Baseline in the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Score
Hide Description EORTC QLQ-C30, a self-reported, cancer-specific instrument assessing 15 domains: physical, role, emotional, cognitive and social functioning, pain,fatigue, nausea and vomiting, insomnia, loss of appetite, constipation, diarrhea, and dyspnea, financial difficulties and a global health status/quality of life (QOF). Functional and symptoms scales were measured on four point Likert scale where 1 = not at all and 4 = very much. Pat. assessed at Screening; Cycle 4 Day 1 and during follow-up 1 M and every 3 M up to 24 months. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline is the most recent, non-missing value prior to or on the first study treatment dose date. Clinically meaningful changes or minimally important differences (MIDs)have been previously established for the EORTC QLQ C30, and categorized as ‘small’ if the mean change in scores is 5-10 points, ‘moderate’ if 10-20 points, and ‘large’ if >20points.
Time Frame Screening, Cycle 3 Day 1, and 1 M and every 3 month post last dose up to 24 month.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed
Arm/Group Title Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Fludarabine + Cyclophosphamide_ ITT Subjects
Hide Arm/Group Description:
Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared [m^2] and cyclophosphamide was administered at 250mg/m^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m^2 and cyclophosphamide administered at 250mg/m^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Overall Number of Participants Analyzed 183 182
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Appetite Loss, Cycle 4 Day 1, n=140, 124 Number Analyzed 140 participants 124 participants
0.5  (25.60) -1.9  (26.65)
Appetite Loss, 1 M, FU, n=136, 119 Number Analyzed 136 participants 119 participants
-0.2  (26.14) -3.9  (28.52)
Appetite Loss, 3 M, FU, n=142, 108 Number Analyzed 142 participants 108 participants
-0.7  (26.77) -7.4  (28.22)
Appetite Loss, 6 M, FU, n=123, 97 Number Analyzed 123 participants 97 participants
-6.0  (23.00) -12.4  (26.05)
Appetite Loss, 9 M, FU, n=112, 83 Number Analyzed 112 participants 83 participants
-3.9  (20.38) -9.6  (25.25)
Appetite Loss. 12 M, FU, n=107, 72 Number Analyzed 107 participants 72 participants
-4.0  (22.76) -6.0  (27.59)
Appetite Loss, 15 M, FU, n=96, 60 Number Analyzed 96 participants 60 participants
-3.8  (23.13) -9.4  (28.19)
Appetite Loss, 18 M, FU, n=89, 60 Number Analyzed 89 participants 60 participants
-7.9  (20.11) -9.4  (30.12)
Appetite Loss, 21 M, FU, n=87, 52 Number Analyzed 87 participants 52 participants
-3.4  (20.36) -7.7  (27.70)
Appetite Loss, 24 M, FU, n=69, 48 Number Analyzed 69 participants 48 participants
-3.9  (22.53) -12.5  (29.68)
Cognitive Functioning, Cycle 4 Day 1, n=142, 126 Number Analyzed 142 participants 126 participants
3.4  (18.25) 2.5  (18.39)
Cognitive Functioning, 1 M, FU, n=139, 122 Number Analyzed 139 participants 122 participants
-0.4  (18.40) 3.0  (19.87)
Cognitive Functioning, 3 M, FU, n= 145, 109 Number Analyzed 145 participants 109 participants
0.0  (18.74) 2.3  (21.69)
Cognitive Functioning, 6 M, FU, n=126, 99 Number Analyzed 126 participants 99 participants
1.7  (18.95) 2.7  (20.99)
Cognitive Functioning, 9 M, FU, n=115, 85 Number Analyzed 115 participants 85 participants
-0.6  (20.58) 2.4  (19.61)
Cognitive Functioning. 12 M, FU, n=110, 76 Number Analyzed 110 participants 76 participants
-2.1  (19.17) -1.8  (21.36)
Cognitive Functioning, 15 M, FU, n=97, 62 Number Analyzed 97 participants 62 participants
-1.0  (17.97) 0.3  (20.58)
Cognitive Functioning, 18 M, FU, n=89, 61 Number Analyzed 89 participants 61 participants
-0.9  (20.00) -0.3  (22.67)
Cognitive Functioning, 21 M, FU, n=88, 53 Number Analyzed 88 participants 53 participants
-1.9  (21.65) -1.9  (21.84)
Cognitive Functioning, 24 M, FU, n=70, 50 Number Analyzed 70 participants 50 participants
1.0  (20.83) -1.3  (21.25)
Constipation, Cycle 4 Day 1, n=142, 126 Number Analyzed 142 participants 126 participants
2.1  (21.46) 0.8  (18.60)
Constipation, 1 M, FU, n=139, 122 Number Analyzed 139 participants 122 participants
-0.7  (19.02) 0.3  (18.92)
Constipation, 3 M, FU, n= 145, 109 Number Analyzed 145 participants 109 participants
-2.1  (19.33) -0.9  (20.01)
Constipation, 6 M, FU, n=125, 98 Number Analyzed 125 participants 98 participants
-3.5  (19.32) 0.3  (18.22)
Constipation, 9 M, FU, n=115, 85 Number Analyzed 115 participants 85 participants
-1.2  (19.71) 0.4  (18.18)
Constipation. 12 M, FU, n=109, 76 Number Analyzed 109 participants 76 participants
-0.0  (23.13) 0.4  (19.24)
Constipation, 15 M, FU, n=96, 62 Number Analyzed 96 participants 62 participants
-1.7  (21.29) -3.8  (20.11)
Constipation, 18 M, FU, n=90, 61 Number Analyzed 90 participants 61 participants
-0.4  (21.49) -1.1  (24.32)
Constipation, 21 M, FU, n=87, 53 Number Analyzed 87 participants 53 participants
-1.9  (22.93) -3.8  (23.26)
Constipation, 24 M, FU, n=70, 50 Number Analyzed 70 participants 50 participants
0.0  (21.23) -3.3  (21.56)
Diarrhoea, Cycle 4 Day 1,n= 141, 125 Number Analyzed 141 participants 125 participants
0.2  (19.72) -2.4  (17.54)
Diarrhoea, 1 M, FU, n=135, 121 Number Analyzed 135 participants 121 participants
-3.5  (20.87) 0.8  (21.28)
Diarrhoea, 3 M, FU, n=143, 109 Number Analyzed 143 participants 109 participants
1.6  (22.49) 1.5  (20.98)
Diarrhoea, 6 M, FU, n=124, 98 Number Analyzed 124 participants 98 participants
0.0  (20.38) -3.1  (16.64)
Diarrhoea, 9 M, FU, n=114, 85 Number Analyzed 114 participants 85 participants
0.3  (20.56) -2.7  (17.97)
Diarrhoea. 12 M, FU, n=108, 76 Number Analyzed 108 participants 76 participants
-3.4  (15.75) -2.2  (19.12)
Diarrhoea, 15 M, FU, n=96, 61 Number Analyzed 96 participants 61 participants
-1.7  (19.57) -4.4  (20.62)
Diarrhoea, 18 M, FU, n=89, 61 Number Analyzed 89 participants 61 participants
-1.9  (17.67) -1.1  (17.18)
Diarrhoea, 21 M, FU, n=87, 53 Number Analyzed 87 participants 53 participants
-2.3  (18.88) 0.6  (21.17)
Diarrhoea, 24 M, FU, n=68, 50 Number Analyzed 68 participants 50 participants
-2.9  (17.02) -0.7  (20.75)
Dyspnoea Cycle 4 Day 1,n= 138, 124 Number Analyzed 138 participants 124 participants
-4.6  (22.85) -4.6  (23.41)
Dyspnoea, 1 M, FU, n=139, 121 Number Analyzed 139 participants 121 participants
-1.0  (26.60) -2.8  (25.67)
Dyspnoea, 3 M, FU, n=141, 108 Number Analyzed 141 participants 108 participants
-3.1  (26.40) -1.5  (25.53)
Dyspnoea, 6 M, FU, n=124, 97 Number Analyzed 124 participants 97 participants
-2.7  (21.92) -7.2  (24.17)
Dyspnoea, 9 M, FU, n=113, 83 Number Analyzed 113 participants 83 participants
-2.7  (26.03) -6.4  (23.55)
Dyspnoea. 12 M, FU, n=108, 73 Number Analyzed 108 participants 73 participants
-3.4  (24.52) -4.1  (22.87)
Dyspnoea, 15 M, FU, n=95, 60 Number Analyzed 95 participants 60 participants
-2.5  (20.77) -2.2  (26.66)
Dyspnoea, 18 M, FU, n=90, 59 Number Analyzed 90 participants 59 participants
-3.0  (24.81) -2.8  (29.22)
Dyspnoea, 21 M, FU, n=87, 52 Number Analyzed 87 participants 52 participants
-3.4  (24.92) -1.9  (21.30)
Dyspnoea, 24 M, FU, n=69, 49 Number Analyzed 69 participants 49 participants
-2.4  (26.39) -4.8  (24.53)
Emotional Functioning Cycle 4 Day 1, n=142, 125 Number Analyzed 142 participants 125 participants
4.4  (17.91) 5.4  (19.59)
Emotional Functioning, 1 M, FU, n=139, 122 Number Analyzed 139 participants 122 participants
5.4  (20.26) 7.2  (24.08)
Emotional Functioning, 3 M, FU, n=145, 109 Number Analyzed 145 participants 109 participants
5.7  (20.93) 7.8  (20.90)
Emotional Functioning, 6 M, FU, n=126, 99 Number Analyzed 126 participants 99 participants
4.8  (22.57) 8.9  (22.34)
Emotional Functioning, 9 M, FU, n=115, 85 Number Analyzed 115 participants 85 participants
3.4  (22.95) 6.7  (18.52)
Emotional Functioning. 12 M, FU, n=110, 76 Number Analyzed 110 participants 76 participants
3.9  (22.11) 8.0  (21.92)
Emotional Functioning, 15 M, FU, n=98, 62 Number Analyzed 98 participants 62 participants
5.1  (21.54) 6.5  (21.15)
Emotional Functioning, 18 M, FU, n=90, 61 Number Analyzed 90 participants 61 participants
5.1  (22.94) 6.5  (26.35)
Emotional Functioning, 21 M, FU, n=88, 52 Number Analyzed 88 participants 52 participants
5.3  (22.43) 7.7  (23.56)
Emotional Functioning, 24 M, FU, n=70, 50 Number Analyzed 70 participants 50 participants
7.1  (23.02) 7.1  (26.16)
Fatigue Cycle 4 Day 1, n=142, 126 Number Analyzed 142 participants 126 participants
-4.3  (21.37) -6.3  (22.66)
Fatigue, 1 M, FU, n=138, 122 Number Analyzed 138 participants 122 participants
-7.4  (25.16) -4.5  (28.64)
Fatigue, 3 M, FU, n=145, 109 Number Analyzed 145 participants 109 participants
-5.4  (24.01) -9.3  (27.83)
Fatigue, 6 M, FU, n=126, 99 Number Analyzed 126 participants 99 participants
-8.2  (23.64) -12.2  (22.43)
Fatigue, 9 M, FU, n=115, 86 Number Analyzed 115 participants 86 participants
-8.8  (23.80) -9.8  (24.56)
Fatigue. 12 M, FU, n=110, 76 Number Analyzed 110 participants 76 participants
-6.8  (25.28) -10.3  (23.44)
Fatigue, 15 M, FU, n=97, 76 Number Analyzed 97 participants 76 participants
-7.6  (19.83) -8.9  (27.61)
Fatigue, 18 M, FU, n=90, 62 Number Analyzed 90 participants 62 participants
-7.0  (22.25) -6.1  (30.15)
Fatigue, 21 M, FU, n=88, 53 Number Analyzed 88 participants 53 participants
-9.6  (20.44) -9.1  (25.34)
Fatigue, 24 M, FU, n=70, 50 Number Analyzed 70 participants 50 participants
-9.1  (23.01) -11.7  (25.30)
Financial Difficulties Cycle 4 Day 1, n=141, 126 Number Analyzed 141 participants 126 participants
-4.5  (23.98) -6.1  (29.93)
Financial Difficulties, 1 M, FU, n=136, 122 Number Analyzed 136 participants 122 participants
-5.9  (26.57) -5.2  (26.07)
Financial Difficulties, 3 M, FU, n=145, 108 Number Analyzed 145 participants 108 participants
-4.1  (28.30) -9.0  (29.40)
Financial Difficulties, 6 M, FU, n=126, 98 Number Analyzed 126 participants 98 participants
-5.8  (24.61) -8.8  (26.89)
Financial Difficulties, 9 M, FU, n=114, 84 Number Analyzed 114 participants 84 participants
-6.1  (27.54) -8.7  (27.44)
Financial Difficulties. 12 M, FU, n=110, 76 Number Analyzed 110 participants 76 participants
-6.4  (24.93) -9.6  (28.71)
Financial Difficulties, 15 M, FU, n=96, 62 Number Analyzed 96 participants 62 participants
-8.3  (23.69) -9.7  (27.91)
Financial Difficulties, 18 M, FU, n=90, 60 Number Analyzed 90 participants 60 participants
-4.1  (24.39) -12.2  (30.04)
Financial Difficulties, 21 M, FU, n=88, 51 Number Analyzed 88 participants 51 participants
-10.6  (22.34) -11.1  (28.02)
Financial Difficulties, 24 M, FU, n=70, 50 Number Analyzed 70 participants 50 participants
-6.2  (24.93) -12.0  (27.57)
Nausea and Vomiting Cycle 4 Day 1, n=142, 126 Number Analyzed 142 participants 126 participants
2.0  (16.06) 3.7  (18.37)
Nausea and Vomiting, 1 M, FU, n=139, 122 Number Analyzed 139 participants 122 participants
1.0  (14.85) 0.1  (19.22)
Nausea and Vomiting, 3 M, FU, n=145, 109 Number Analyzed 145 participants 109 participants
0.1  (15.90) -2.9  (14.49)
Nausea and Vomiting, 6 M, FU, n=126, 99 Number Analyzed 126 participants 99 participants
-2.8  (13.12) -2.5  (14.36)
Nausea and Vomiting, 9 M, FU, n=115, 86 Number Analyzed 115 participants 86 participants
-1.3  (13.81) -1.2  (15.08)
Nausea and Vomiting. 12 M, FU, n=110, 76 Number Analyzed 110 participants 76 participants
-2.9  (13.52) -1.8  (12.35)
Nausea and Vomiting, 15 M, FU, n=97, 62 Number Analyzed 97 participants 62 participants
-3.3  (11.45) -2.7  (11.76)
Nausea and Vomiting, 18 M, FU, n=90, 61 Number Analyzed 90 participants 61 participants
-3.3  (12.03) -2.5  (10.02)
Nausea and Vomiting, 21 M, FU, n=88, 53 Number Analyzed 88 participants 53 participants
-4.0  (13.37) 1.3  (11.72)
Nausea and Vomiting, 24 M, FU, n=70, 50 Number Analyzed 70 participants 50 participants
-2.4  (13.69) -0.3  (11.90)
Pain Cycle 4 Day 1, n=142, 126 Number Analyzed 142 participants 126 participants
-3.6  (20.64) -4.2  (20.43)
Pain, 1 M, FU, n=139, 122 Number Analyzed 139 participants 122 participants
-2.8  (23.02) -5.5  (22.31)
Pain, 3 M, FU, n=145, 109 Number Analyzed 145 participants 109 participants
-3.8  (25.13) -2.1  (24.44)
Pain, 6 M, FU, n=126, 99 Number Analyzed 126 participants 99 participants
-5.3  (23.54) -6.6  (20.59)
Pain, 9 M, FU, n=115, 86 Number Analyzed 115 participants 86 participants
-4.2  (23.86) -4.8  (22.12)
Pain. 12 M, FU, n=110, 76 Number Analyzed 110 participants 76 participants
-3.5  (24.43) -3.7  (21.01)
Pain, 15 M, FU, n=98, 62 Number Analyzed 98 participants 62 participants
-2.9  (23.08) -3.5  (22.00)
Pain, 18 M, FU, n=90, 61 Number Analyzed 90 participants 61 participants
-3.3  (19.39) 0.5  (28.05)
Pain, 21 M, FU, n=88, 53 Number Analyzed 88 participants 53 participants
-5.9  (19.74) -0.9  (25.82)
Pain, 24 M, FU, n=70, 50 Number Analyzed 70 participants 50 participants
-1.7  (23.25) -3.0  (24.67)
Physical Functioning Cycle 4 Day 1, n=141, 124 Number Analyzed 141 participants 124 participants
1.2  (14.50) 0.6  (16.81)
Physical Functioning, 1 M, FU, n=139, 122 Number Analyzed 139 participants 122 participants
0.4  (19.52) -0.7  (21.15)
Physical Functioning, 3 M, FU, n=142, 108 Number Analyzed 142 participants 108 participants
0.9  (18.66) 0.9  (19.68)
Physical Functioning, 6 M, FU, n=124, 98 Number Analyzed 124 participants 98 participants
3.2  (16.41) 5.7  (17.01)
Physical Functioning, 9 M, FU, n=113, 83 Number Analyzed 113 participants 83 participants
3.9  (17.30) 6.2  (17.25)
Physical Functioning. 12 M, FU, n=109, 73 Number Analyzed 109 participants 73 participants
2.4  (17.98) 3.5  (17.52)
Physical Functioning, 15 M, FU, n=96, 60 Number Analyzed 96 participants 60 participants
3.8  (14.65) 2.7  (18.46)
Physical Functioning, 18 M, FU, n=90, 60 Number Analyzed 90 participants 60 participants
4.1  (16.65) 0.1  (22.09)
Physical Functioning, 21 M, FU, n=88, 52 Number Analyzed 88 participants 52 participants
4.7  (17.14) 2.1  (18.88)
Physical Functioning, 24 M, FU, n=69, 49 Number Analyzed 69 participants 49 participants
5.3  (17.44) 3.7  (20.57)
Global Health Status Cycle 4 Day 1, n=140, 122 Number Analyzed 140 participants 122 participants
6.4  (23.46) 6.8  (17.54)
Global Health Status, 1 M, FU, n=136, 119 Number Analyzed 136 participants 119 participants
6.5  (24.23) 6.9  (26.32)
Global Health Status, 3 M, FU, n=142, 105 Number Analyzed 142 participants 105 participants
5.0  (21.45) 12.3  (21.15)
Global Health Status, 6 M, FU, n=125, 97 Number Analyzed 125 participants 97 participants
7.5  (21.57) 13.7  (23.01)
Global Health Status, 9 M, FU, n=112, 83 Number Analyzed 112 participants 83 participants
7.6  (23.24) 11.7  (22.35)
Global Health Status. 12 M, FU, n=110, 74 Number Analyzed 110 participants 74 participants
7.6  (23.64) 12.2  (21.77)
Global Health Status, 15 M, FU, n=93, 61 Number Analyzed 93 participants 61 participants
7.6  (20.40) 12.7  (22.29)
Global Health Status, 18 M, FU, n= 89, 60 Number Analyzed 89 participants 60 participants
9.2  (23.03) 10.4  (27.00)
Global Health Status, 21 M, FU, n=87, 53 Number Analyzed 87 participants 53 participants
10.8  (20.26) 12.7  (21.53)
Global Health Status, 24 M, FU, n=68, 48 Number Analyzed 68 participants 48 participants
12.1  (24.28) 12.3  (24.31)
Role Functioning Cycle 4 Day 1,n=140, 124 Number Analyzed 140 participants 124 participants
1.4  (23.27) 0.1  (24.83)
Role Functioning, 1 M, FU, n= 138, 120 Number Analyzed 138 participants 120 participants
-0.1  (25.83) -0.7  (27.53)
Role Functioning, 3 M, FU, n=141, 107 Number Analyzed 141 participants 107 participants
0.5  (25.19) 0.9  (28.94)
Role Functioning, 6 M, FU, n=124, 97 Number Analyzed 124 participants 97 participants
4.3  (25.49) 5.5  (26.54)
Role Functioning, 9 M, FU, n=113, 83 Number Analyzed 113 participants 83 participants
4.1  (26.21) 6.2  (25.60)
Role Functioning. 12 M, FU, n=109, 72 Number Analyzed 109 participants 72 participants
2.1  (26.46) 3.9  (24.78)
Role Functioning, 15 M, FU, n=96, 60 Number Analyzed 96 participants 60 participants
3.8  (24.84) 1.9  (25.13)
Role Functioning, 18 M, FU, n=90, 60 Number Analyzed 90 participants 60 participants
7.0  (24.09) -0.0  (28.95)
Role Functioning, 21 M, FU, n=88, 51 Number Analyzed 88 participants 51 participants
5.3  (22.82) 2.6  (26.74)
Role Functioning, 24 M, FU, n=69, 49 Number Analyzed 69 participants 49 participants
5.8  (25.54) 3.7  (30.10)
Social Functioning Cycle 4 Day 1, n=142, 126 Number Analyzed 142 participants 126 participants
3.1  (20.30) -0.9  (23.50)
Social Functioning, 1 M, FU, n=138, 122 Number Analyzed 138 participants 122 participants
0.4  (25.98) 0.8  (27.93)
Social Functioning, 3 M, FU, n=145, 109 Number Analyzed 145 participants 109 participants
0.8  (23.76) 4.3  (26.29)
Social Functioning, 6 M, FU, n= 126, 99 Number Analyzed 126 participants 99 participants
3.4  (22.04) 6.1  (26.24)
Social Functioning, 9 M, FU, n=115, 84 Number Analyzed 115 participants 84 participants
2.3  (21.84) 4.2  (25.46)
Social Functioning. 12 M, FU, n= 110, 76 Number Analyzed 110 participants 76 participants
3.0  (23.04) 3.3  (21.95)
Social Functioning, 15 M, FU, n=96, 62 Number Analyzed 96 participants 62 participants
6.2  (18.30) 1.6  (27.61)
Social Functioning, 18 M, FU, n=90, 61 Number Analyzed 90 participants 61 participants
6.5  (19.78) 2.7  (29.69)
Social Functioning, 21 M, FU, n=88, 52 Number Analyzed 88 participants 52 participants
6.6  (18.83) 4.5  (24.72)
Social Functioning, 24 M, FU, n=70, 50 Number Analyzed 70 participants 50 participants
7.9  (19.60) 7.7  (24.56)
Insomnia Cycle 4 Day 1, n=138, 123 Number Analyzed 138 participants 123 participants
-3.1  (26.07) -8.7  (26.94)
Insomnia, 1 M, FU, n=135, 120 Number Analyzed 135 participants 120 participants
-5.9  (29.04) -11.1  (27.78)
Insomnia, 3 M, FU, n=139, 108 Number Analyzed 139 participants 108 participants
-6.2  (29.64) -13.3  (28.07)
Insomnia, 6 M, FU, n=121, 98 Number Analyzed 121 participants 98 participants
-5.2  (26.18) -17.0  (25.88)
Insomnia, 9 M, FU, n=112, 81 Number Analyzed 112 participants 81 participants
-3.0  (30.53) -13.2  (31.04)
Insomnia. 12 M, FU, n=106, 73 Number Analyzed 106 participants 73 participants
-6.9  (25.91) -10.5  (29.33)
Insomnia, 15 M, FU, n=96, 59 Number Analyzed 96 participants 59 participants
-5.9  (29.02) -17.5  (26.52)
Insomnia, 18 M, FU, n=89, 59 Number Analyzed 89 participants 59 participants
-7.5  (28.32) -15.3  (28.58)
Insomnia, 21 M, FU, n=86, 52 Number Analyzed 86 participants 52 participants
-8.5  (25.15) -10.3  (34.64)
Insomnia, 24 M, FU, n=68, 49 Number Analyzed 68 participants 49 participants
-1.5  (33.30) -13.6  (35.95)
26.Secondary Outcome
Title Mean of Health Change Questionnaire (HCQ)
Hide Description The HCQ consists of a single question in which the participant is asked if he/she has experienced any change in his/her health overall since beginning the study. For HCQ, values from 1 to 9 were assigned to the 9 responses in the HCQ questionnaire, ranging from 1 for ‘my health is a great deal better’ to 9 for ‘my health is a great deal worse’ since the beginning of the study. Lower scores represent better conditions.
Time Frame Screening, Cycle 3 Day 1, and 1 M and every 3 month post last dose up to 24 month.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Fludarabine + Cyclophosphamide_ ITT Subjects
Hide Arm/Group Description:
Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared [m^2] and cyclophosphamide was administered at 250mg/m^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m^2 and cyclophosphamide administered at 250mg/m^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Overall Number of Participants Analyzed 183 182
Mean (Standard Deviation)
Unit of Measure: Unit on a scale
Cycle 4 Day 1, n=139, 124 Number Analyzed 139 participants 124 participants
2.6  (1.62) 2.8  (1.59)
1 M, FU, n=138, 121 Number Analyzed 138 participants 121 participants
3.0  (2.05) 3.2  (2.30)
3 M, FU, n=141, 108 Number Analyzed 141 participants 108 participants
3.0  (2.11) 2.8  (1.86)
6 M, FU, n=124, 98 Number Analyzed 124 participants 98 participants
2.6  (1.76) 2.6  (1.82)
9 M, FU, n=112, 85 Number Analyzed 112 participants 85 participants
2.5  (1.78) 2.4  (1.57)
12 M, FU, n=108, 74 Number Analyzed 108 participants 74 participants
2.5  (1.80) 2.5  (1.78)
15 M, FU, n=96, 61 Number Analyzed 96 participants 61 participants
2.2  (1.57) 2.3  (1.68)
18 M, FU, n=88, 58 Number Analyzed 88 participants 58 participants
2.4  (1.67) 2.7  (2.01)
21 M, FU, n= 87, 52 Number Analyzed 87 participants 52 participants
2.3  (1.50) 2.3  (1.52)
24 M, FU, n=69, 49 Number Analyzed 69 participants 49 participants
2.3  (1.76) 2.6  (1.89)
27.Secondary Outcome
Title Mean Area Under the Time-concentration Curve (AUC) Curve Over the Dosing Interval (AUC[0-tau]) of Ofatumumab
Hide Description Area under the time-concentration curve (AUC) over the dosing interval (AUC[0-tau]) was evaluated. Blood samples were collected from participants who received ofatumumab plus fludarabine and cyclophosphamide predose and 0.5 h after the end of the ofatumumab infusion at treatment Cycle 1 and Cycle 4 (Days 1, 8, and 85). In addition, predose samples were collected prior to ofatumumab administration at Cycles 2, 3, 5, and 6 (Days 29, 57, 113, and 141).
Time Frame Cycle 1 Week 1, Cycle 1 Week 2, Cycles 2,3,4,5,6
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Hide Analysis Population Description
PK Population: Participants for whom a pharmacokinetic sample was obtained were analyzed, only participants available at the specified time points were analyzed(represented by n=X in the category titles)
Arm/Group Title Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects
Hide Arm/Group Description:
Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared [m^2] and cyclophosphamide was administered at 250mg/m^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Overall Number of Participants Analyzed 183
Geometric Mean (95% Confidence Interval)
Unit of Measure: hour*nanogram/mililiter (h*ng/mL)
cycle 1, week 1, n=158 Number Analyzed 158 participants
3554.910
(3224.844 to 3918.759)
cycle 1, week 2, n=129 Number Analyzed 129 participants
34109.67
(30042.08 to 38728.00)
cycle 2, n=147 Number Analyzed 147 participants
67069.79
(59485.45 to 75621.13)
cycle 3, n=129 Number Analyzed 129 participants
84620.05
(76209.86 to 93958.35)
cycle 4, 107 Number Analyzed 107 participants
89091.35
(78326.34 to 101335.9)
cycle 5, n=97 Number Analyzed 97 participants
96829.23
(84488.81 to 110972.1)
cycle 6, n=91 Number Analyzed 91 participants
104798.0
(90904.74 to 120814.6)
28.Secondary Outcome
Title Maximum Concentration (Cmax) and Observed Drug Concentration Prior to the Next Dose (Ctrough) of Ofatumumab
Hide Description Blood samples were collected to assess the plasma concentration of ofatumumab.Cmax and Ctrough were determined. Blood samples were collected from participants who received ofatumumab plus fludarabine and cyclophosphamide predose and 0.5 h after the end of the ofatumumab infusion at treatment Cycle 1 and Cycle 4 (Days 1, 8, and 85). In addition, predose samples were collected prior to ofatumumab administration at Cycles 2, 3, 5, and 6 (Days 29, 57, 113, and 141).
Time Frame Cycle 1 Week 1, Cycle 1 Week 2, Cycles 2,3,4,5
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK Population: Participants for whom a pharmacokinetic sample was obtained were analyzed, only participants available at the specified time points were analyzed(represented by n=X in the category titles)
Arm/Group Title Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects
Hide Arm/Group Description:
Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared [m^2] and cyclophosphamide was administered at 250mg/m^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Overall Number of Participants Analyzed 183
Geometric Mean (95% Confidence Interval)
Unit of Measure: Micrograms per milliliter
Cmax cycle 1, week 1, n=154 Number Analyzed 154 participants
61.355
(55.444 to 67.897)
Cmax cycle 1, week 2, n=159 Number Analyzed 159 participants
241.192
(210.492 to 276.369)
Cmax cycle 4, n=140 Number Analyzed 140 participants
312.745
(287.708 to 339.961)
Ctrough cycle 1, week 1, n=167 Number Analyzed 167 participants
3.551
(2.417 to 5.217)
Ctrough cycle 1, week 2, n=165 Number Analyzed 165 participants
9.496
(6.565 to 13.736)
Ctrough cycle 2, n=162 Number Analyzed 162 participants
24.281
(17.953 to 32.840)
Ctrough cycle 3,n=150 Number Analyzed 150 participants
25.632
(18.884 to 34.791)
Ctrough cycle 4,n=130 Number Analyzed 130 participants
58.640
(44.465 to 77.333)
Ctrough cycle 5, n=113 Number Analyzed 113 participants
70.398
(55.257 to 89.686)
29.Secondary Outcome
Title Time of Occurrence of Cmax (Tmax) of Ofatumumab
Hide Description Blood samples were collected from participants who received ofatumumab plus fludarabine and cyclophosphamide predose and 0.5 h after the end of the ofatumumab infusion at treatment Cycle 1 and Cycle 4.
Time Frame Cycle 1 Week 1, Cycle 1 Week 2, Cycle 4
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK Population: Participants for whom a pharmacokinetic sample was obtained were analyzed, only participants available at the specified time points were analyzed(represented by n=X in the category titles)
Arm/Group Title Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects
Hide Arm/Group Description:
Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared [m^2] and cyclophosphamide was administered at 250mg/m^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
Overall Number of Participants Analyzed 183
Geometric Mean (95% Confidence Interval)
Unit of Measure: Hour
cycle 1, week 1,n=154 Number Analyzed 154 participants
6.106
(5.789 to 6.442)
cycle 1, week 2, n=159 Number Analyzed 159 participants
5.004
(4.896 to 5.114)
cycle 4, n=140 Number Analyzed 140 participants
4.878
(4.661 to 5.105)
Time Frame Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 5 years.
Adverse Event Reporting Description Analysis was done in the safety Population included subjects who received at least one dose of a study drug. This population was used for all safety measurements. In the analyses, subjects were grouped based on the treatment they receive regardless of how they are randomized.
 
Arm/Group Title Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Fludarabine + Cyclophosphamide_ ITT Subjects
Hide Arm/Group Description Participants with relapsed CLL received IV infusions of ofatumumab in combination with fludarabine and cyclophosphamide IV infusions for 6 cycles; each cycle comprised of 28 days. Participants received ofatumumab administered at 300 milligram (mg) on Day 1, 1000 mg on Day 8 of cycle 1 and 1000 mg on Day 1 of cycles 2, 3, 4, 5 and 6. Fludarabine was administered at 25 mg/meter squared [m^2] and cyclophosphamide was administered at 250mg/m^2 on Days 1-3 of each cycles (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status. Participants with relapsed CLL received IV infusions of fludarabine administered at 25 mg/m^2 and cyclophosphamide administered at 250mg/m^2 on Days 1-3 of each cycle (6 cycles). Participants were followed up one month post therapy and every 3 months for 5 years to evaluate survival and disease status.
All-Cause Mortality
Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Fludarabine + Cyclophosphamide_ ITT Subjects
Affected / at Risk (%) Affected / at Risk (%)
Total   40/181 (22.10%)   42/178 (23.60%) 
Show Serious Adverse Events Hide Serious Adverse Events
Ofatumumab + Fludarabine + Cyclophosphamide_ ITT Subjects Fludarabine + Cyclophosphamide_ ITT Subjects
Affected / at Risk (%) Affected / at Risk (%)
Total   108/181 (59.67%)   86/178 (48.31%) 
Blood and lymphatic system disorders     
Agranulocytosis  1  0/181 (0.00%)  2/178 (1.12%) 
Anaemia  1  11/181 (6.08%)  12/178 (6.74%) 
Aplasia pure red cell  1  1/181 (0.55%)  0/178 (0.00%) 
Autoimmune haemolytic anaemia  1  2/181 (1.10%)  2/178 (1.12%) 
Febrile neutropenia  1  18/181 (9.94%)  15/178 (8.43%) 
Granulocytopenia  1  1/181 (0.55%)  0/178 (0.00%) 
Haemolysis  1  0/181 (0.00%)  1/178 (0.56%) 
Haemolytic anaemia  1  0/181 (0.00%)  2/178 (1.12%) 
Immune thrombocytopenic purpura  1  0/181 (0.00%)  2/178 (1.12%) 
Leukopenia  1  2/181 (1.10%)  1/178 (0.56%) 
Lymphadenopathy  1  1/181 (0.55%)  0/178 (0.00%) 
Neutropenia  1  17/181 (9.39%)  14/178 (7.87%) 
Pancytopenia  1  5/181 (2.76%)  5/178 (2.81%) 
Thrombocytopenia  1  7/181 (3.87%)  10/178 (5.62%) 
Cardiac disorders     
Acute myocardial infarction  1  2/181 (1.10%)  2/178 (1.12%) 
Angina pectoris  1  0/181 (0.00%)  2/178 (1.12%) 
Atrial fibrillation  1  2/181 (1.10%)  3/178 (1.69%) 
Bradycardia  1  0/181 (0.00%)  1/178 (0.56%) 
Cardiac arrest  1  1/181 (0.55%)  1/178 (0.56%) 
Cardiac failure  1  1/181 (0.55%)  1/178 (0.56%) 
Cardiac failure acute  1  0/181 (0.00%)  4/178 (2.25%) 
Cardiac failure congestive  1  0/181 (0.00%)  1/178 (0.56%) 
Cardiopulmonary failure  1  0/181 (0.00%)  1/178 (0.56%) 
Coronary artery disease  1  1/181 (0.55%)  1/178 (0.56%) 
Extrasystoles  1  0/181 (0.00%)  1/178 (0.56%) 
Myocardial infarction  1  0/181 (0.00%)  1/178 (0.56%) 
Myocardial ischaemia  1  1/181 (0.55%)  1/178 (0.56%) 
Pericardial effusion  1  0/181 (0.00%)  1/178 (0.56%) 
Tachycardia paroxysmal  1  0/181 (0.00%)  1/178 (0.56%) 
Congenital, familial and genetic disorders     
Epidermolysis  1  1/181 (0.55%)  0/178 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  1  1/181 (0.55%)  0/178 (0.00%) 
Abdominal pain upper  1  1/181 (0.55%)  0/178 (0.00%) 
Anal fistula  1  0/181 (0.00%)  1/178 (0.56%) 
Ascites  1  0/181 (0.00%)  1/178 (0.56%) 
Colitis  1  1/181 (0.55%)  1/178 (0.56%) 
Constipation  1  2/181 (1.10%)  0/178 (0.00%) 
Diarrhoea  1  3/181 (1.66%)  3/178 (1.69%) 
Gastrointestinal haemorrhage  1  3/181 (1.66%)  1/178 (0.56%) 
Gastrooesophageal reflux disease  1  1/181 (0.55%)  1/178 (0.56%) 
Ileus  1  1/181 (0.55%)  0/178 (0.00%) 
Ileus paralytic  1  1/181 (0.55%)  0/178 (0.00%) 
Inguinal hernia  1  2/181 (1.10%)  0/178 (0.00%) 
Mouth ulceration  1  1/181 (0.55%)  0/178 (0.00%) 
Nausea  1  2/181 (1.10%)  0/178 (0.00%) 
Oesophagitis  1  0/181 (0.00%)  2/178 (1.12%) 
Proctalgia  1  1/181 (0.55%)  0/178 (0.00%) 
Salivary hypersecretion  1  1/181 (0.55%)  0/178 (0.00%) 
Stomatitis  1  1/181 (0.55%)  0/178 (0.00%) 
Vomiting  1  1/181 (0.55%)  1/178 (0.56%) 
General disorders     
Asthenia  1  0/181 (0.00%)  1/178 (0.56%) 
Chills  1  1/181 (0.55%)  0/178 (0.00%) 
Death  1  3/181 (1.66%)  1/178 (0.56%) 
Fatigue  1  1/181 (0.55%)  0/178 (0.00%) 
General physical health deterioration  1  0/181 (0.00%)  2/178 (1.12%) 
Hyperthermia  1  1/181 (0.55%)  0/178 (0.00%) 
Malaise  1  0/181 (0.00%)  1/178 (0.56%) 
Oedema peripheral  1  1/181 (0.55%)  2/178 (1.12%) 
Pyrexia  1  9/181 (4.97%)  5/178 (2.81%) 
Sudden death  1  0/181 (0.00%)  1/178 (0.56%) 
Hepatobiliary disorders     
Cholecystitis  1  1/181 (0.55%)  0/178 (0.00%) 
Hepatic failure  1  2/181 (1.10%)  0/178 (0.00%) 
Hepatic function abnormal  1  0/181 (0.00%)  1/178 (0.56%) 
Hepatitis  1  2/181 (1.10%)  0/178 (0.00%) 
Hyperbilirubinaemia  1  1/181 (0.55%)  0/178 (0.00%) 
Immune system disorders     
Anaphylactic reaction  1  1/181 (0.55%)  0/178 (0.00%) 
Graft versus host disease  1  0/181 (0.00%)  1/178 (0.56%) 
Infections and infestations     
Acinetobacter bacteraemia  1  0/181 (0.00%)  1/178 (0.56%) 
Acinetobacter infection  1  0/181 (0.00%)  1/178 (0.56%) 
Anal abscess  1  0/181 (0.00%)  1/178 (0.56%) 
Appendicitis  1  1/181 (0.55%)  0/178 (0.00%) 
Atypical mycobacterial infection  1  0/181 (0.00%)  1/178 (0.56%) 
Atypical pneumonia  1  0/181 (0.00%)  1/178 (0.56%) 
Bacteraemia  1  0/181 (0.00%)  1/178 (0.56%) 
Bacterial infection  1  0/181 (0.00%)  1/178 (0.56%) 
Bacterial sepsis  1  0/181 (0.00%)  1/178 (0.56%) 
Bronchitis  1  3/181 (1.66%)  2/178 (1.12%) 
Campylobacter gastroenteritis  1  0/181 (0.00%)  1/178 (0.56%) 
Campylobacter infection  1  0/181 (0.00%)  1/178 (0.56%) 
Cellulitis  1  2/181 (1.10%)  2/178 (1.12%) 
Clostridium difficile colitis  1  0/181 (0.00%)  1/178 (0.56%) 
Cytomegalovirus infection  1  1/181 (0.55%)  1/178 (0.56%) 
Device related infection  1  1/181 (0.55%)  1/178 (0.56%) 
Diarrhoea infectious  1  1/181 (0.55%)  0/178 (0.00%) 
Diverticulitis  1  1/181 (0.55%)  0/178 (0.00%) 
Endocarditis  1  0/181 (0.00%)  1/178 (0.56%) 
Enterococcal sepsis  1  1/181 (0.55%)  0/178 (0.00%) 
Epididymitis  1  1/181 (0.55%)  0/178 (0.00%) 
Erysipelas  1  1/181 (0.55%)  0/178 (0.00%) 
Escherichia infection  1  0/181 (0.00%)  1/178 (0.56%) 
Escherichia urinary tract infection  1  1/181 (0.55%)  0/178 (0.00%) 
Febrile infection  1  1/181 (0.55%)  1/178 (0.56%) 
Gastroenteritis  1  0/181 (0.00%)  2/178 (1.12%) 
Gastroenteritis salmonella  1  2/181 (1.10%)  0/178 (0.00%) 
Gastrointestinal candidiasis  1  0/181 (0.00%)  1/178 (0.56%) 
H1N1 influenza  1  0/181 (0.00%)  1/178 (0.56%) 
Hepatitis B  1  1/181 (0.55%)  1/178 (0.56%) 
Hepatitis B reactivation  1  1/181 (0.55%)  0/178 (0.00%) 
Herpes zoster  1  1/181 (0.55%)  2/178 (1.12%) 
Infected skin ulcer  1  0/181 (0.00%)  1/178 (0.56%) 
Infection  1  1/181 (0.55%)  1/178 (0.56%) 
Infective exacerbation of bronchiectasis  1  1/181 (0.55%)  0/178 (0.00%) 
Intervertebral discitis  1  1/181 (0.55%)  0/178 (0.00%) 
Lower respiratory tract infection  1  6/181 (3.31%)  2/178 (1.12%)