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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 : January 12, 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

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants (par) were screened within 14 days prior to the start of study drug administration to determine eligibility.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
Ofatumumab + Fludarabine + Cyclophosphamide 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.
Fludarabine + Cyclophosphamide 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.

Participant Flow:   Overall Study
    Ofatumumab + Fludarabine + Cyclophosphamide   Fludarabine + Cyclophosphamide
STARTED   183   182 
COMPLETED   119   102 
NOT COMPLETED   64   80 
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 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Ofatumumab + Fludarabine + Cyclophosphamide 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.
Fludarabine + Cyclophosphamide 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 Total of all reporting groups

Baseline Measures
   Ofatumumab + Fludarabine + Cyclophosphamide   Fludarabine + Cyclophosphamide   Total 
Overall Participants Analyzed 
[Units: Participants]
 183   182   365 
Age 
[Units: Years]
Mean (Standard Deviation)
 61.4  (8.82)   61.6  (10.21)   61.5  (9.52) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      79  43.2%      66  36.3%      145  39.7% 
Male      104  56.8%      116  63.7%      220  60.3% 
Race/Ethnicity, Customized 
[Units: Participants]
     
African American/African Heritage   3   5   8 
American Indian or Alaska Native   3   1   4 
Asian - Central/South Asian Heritage   13   16   29 
Asian - East Asian Heritage   3   3   6 
Asian - South East Asian Heritage   3   3   6 
White - Arabic/North African Heritage   0   1   1 
White - White/Caucasian/European Heritage   158   153   311 


  Outcome Measures

1.  Primary:   Progression-free Survival (PFS), as Assessed by the Independent Review Committee (IRC)   [ Time Frame: From randomization up to 5 years after last dose of study drug ]

2.  Secondary:   Overall Survival (OS)   [ Time Frame: From randomization up to 5 years after last dose of study drug ]

3.  Secondary:   Time to Response, as Assessed by the IRC   [ Time Frame: From randomization up to 5 years after last dose of study drug ]

4.  Secondary:   Duration of Response (DOR), as Assessed by the IRC   [ 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) ]

5.  Secondary:   Time to Progression, as Assessed by the IRC   [ Time Frame: From randomization up to 5 years after the last dose of study drug ]

6.  Secondary:   Time to Next Therapy   [ 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) ]

7.  Secondary:   Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status   [ 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, then every 3 month up to 5 year (up to 60 months) ]

8.  Secondary:   Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time   [ 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, then every 3 M up to 5 year (up to 60 months) ]

9.  Secondary:   Percentage of Participants With the Best Overall Response (OR), as Assessed by the IRC   [ Time Frame: From randomization up to 5 years after last dose of study drug ]

10.  Secondary:   Percentage of Participants With the Best OR, as Assessed by the Investigator   [ Time Frame: From randomization up to 5 years after last dose of study drug ]

11.  Secondary:   Number of Participants Who Were Negative for Minimal Residual Disease (MRD) Assessed by IRC   [ Time Frame: From randomization up to 5 years after last dose of study drug ]

12.  Secondary:   Number of Participants Who Were Negative for MRD Assessed by Investigator   [ Time Frame: From randomization up to 5 years after last dose of study drug ]

13.  Secondary:   Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)   [ 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) ]

14.  Secondary:   Number of Participants With a Human Anti-human Antibody (HAHA) Positive Result at Indicated Time Points   [ Time Frame: From start of study drug until 60 days after the last dose of study medication ]

15.  Secondary:   Number of Participants With Autoimmune Hemolytic Anaemia (AIHA)   [ 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) ]

16.  Secondary:   Number of Participants With Drug Related AEs and SAEs of Maximum Severity of Grade 3 or Higher   [ 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) ]

17.  Secondary:   Number of Participants With at Least One Grade 3/Grade 4 Myelosuppression (Anemia, Neutropenia, and Thrombocytopenia)   [ 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) ]

18.  Secondary:   Number of Participants Who Received no Transfusion or at Least One Transfusion During the Study   [ Time Frame: From randomization up to 5 years after last dose of study drug ]

19.  Secondary:   Mean Level of Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM   [ Time Frame: Baseline, 1M and 6M follow up ]

20.  Secondary:   Change From Baseline in Cluster of Differentiation (CD) Cell Counts, CD5+ and CD19+   [ 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 ]

21.  Secondary:   Change From Baseline in Cell Counts, CD5- CD19+   [ 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 ]

22.  Secondary:   Prognostic and Biological Markers Correlating With Clinical Response   [ Time Frame: From randomization up to 5 years after last dose of study drug ]

23.  Secondary:   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)   [ Time Frame: Screening, Cycle 3 Day 1, and 1 M and every 3 month post last dose up to 24 month. ]

24.  Secondary:   Change From Baseline in Patient Reported Outcome (PRO) as Assessed by EuroQoL Five-Dimension (EQ-5D) Score at Indicated Visit   [ Time Frame: Screening, Cycle 3 Day 1, and 1 M and every 3 month post last dose up to 24 month. ]

25.  Secondary:   Change From Baseline in the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Score   [ Time Frame: Screening, Cycle 3 Day 1, and 1 M and every 3 month post last dose up to 24 month. ]

26.  Secondary:   Mean of Health Change Questionnaire (HCQ)   [ Time Frame: Screening, Cycle 3 Day 1, and 1 M and every 3 month post last dose up to 24 month. ]

27.  Secondary:   Mean Area Under the Time-concentration Curve (AUC) Curve Over the Dosing Interval (AUC[0-tau]) of Ofatumumab   [ Time Frame: Cycle 1 Week 1, Cycle 1 Week 2, Cycles 2,3,4,5,6 ]

28.  Secondary:   Maximum Concentration (Cmax) and Observed Drug Concentration Prior to the Next Dose (Ctrough) of Ofatumumab   [ Time Frame: Cycle 1 Week 1, Cycle 1 Week 2, Cycles 2,3,4,5 ]

29.  Secondary:   Time of Occurrence of Cmax (Tmax) of Ofatumumab   [ Time Frame: Cycle 1 Week 1, Cycle 1 Week 2, Cycle 4 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Clinical Disclosure Office
Organization: Novartis Pharmaceuticals
phone: 862-778-8300


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00824265     History of Changes
Other Study ID Numbers: 110913
First Submitted: January 15, 2009
First Posted: January 16, 2009
Results First Submitted: August 10, 2015
Results First Posted: July 25, 2016
Last Update Posted: January 12, 2018