Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

HuMax-CD20 in B-Cell Chronic Lymphocytic Leukemia (B-CLL) Patients Failing Fludarabine and Alemtuzumab

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00349349
First received: July 6, 2006
Last updated: May 29, 2014
Last verified: June 2013
Results First Received: October 20, 2011  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Leukaemia, Lymphocytic, Chronic
Intervention: Drug: ofatumumab

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
2000 mg Ofatumumab + DR Ofatumumab intravenous (iv) infusion was initiated at 300 milligrams (mg), followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The independent endpoint review committee (IRC) classified these participants as double refractory (DR), defined as participants who were enrolled in the study and were refractory to both fludarabine and alemtuzumab.
2000 mg Ofatumumab + BFR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as bulky fludarabine refractory (BFR), defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy.
2000 mg Ofatumumab + Other Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as "other," defined as participants who were enrolled in the study but did not meet criteria for DR or BFR.

Participant Flow:   Overall Study
    2000 mg Ofatumumab + DR   2000 mg Ofatumumab + BFR   2000 mg Ofatumumab + Other
STARTED   95   112   16 
COMPLETED   42   50   10 
NOT COMPLETED   53   62   6 
Adverse Event                5                6                2 
Withdrawal by Subject                5                2                1 
Withdrawn due to Disease Progression                27                37                1 
Death                13                10                1 
Other Treatment Selected                2                0                0 
Participant Reduced General Condition                0                1                0 
Physician Decision                1                2                1 
No Response                0                3                0 
New Malignancy (Bladder Cancer)                0                1                0 



  Baseline Characteristics
  Hide 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
2000 mg Ofatumumab + DR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as DR, defined as participants who were enrolled in the study and were refractory to both fludarabine and alemtuzumab.
2000 mg Ofatumumab + BFR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as BFR, defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy.
2000 mg Ofatumumab + Other Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as "other,"defined as participants who were enrolled in the study but did not meet criteria for DR or BFR.
Total Total of all reporting groups

Baseline Measures
   2000 mg Ofatumumab + DR   2000 mg Ofatumumab + BFR   2000 mg Ofatumumab + Other   Total 
Overall Participants Analyzed 
[Units: Participants]
 95   112   16   223 
Age 
[Units: Years]
Mean (Standard Deviation)
 63.2  (8.4)   64.4  (9.3)   64.5  (7.4)   63.9  (8.8) 
Gender 
[Units: Participants]
       
Female   24   31   5   60 
Male   71   81   11   163 
Race/Ethnicity, Customized 
[Units: Participants]
       
Asian   1   0   1   2 
Black or African American   2   1   0   3 
Hispanic or Latino   1   0   0   1 
White   88   111   15   214 
Arab   1   0   0   1 
Yemenite   1   0   0   1 
Middle Eastern   1   0   0   1 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants (Par.) Classified as Responders and Non-responders for Objective Response as Assessed by an Independent Endpoint Review Committee (IRC) in Accordance With the National Cancer Institute Working Group (NCIWG) 1996 Guidelines   [ Time Frame: Start of treatment (Week 0 of Visit 2) until Week 24 ]

2.  Secondary:   Duration of Response   [ Time Frame: Start of treatment (Week 0 of Visit 2) until Week 24 ]

3.  Secondary:   Progression-Free Survival (PFS)   [ Time Frame: Start of treatment (Week 0 of Visit 2) until Week 24 ]

4.  Secondary:   Time to Next Chronic Lymphocytic Leukemia (CLL) Treatment   [ Time Frame: Time from randomization (Week 0 of Visit 2) until the time of first administration of a CLL treatment other than ofatumumab (assessed for a median of 8.7 weeks currently [or up to 13.3 months]) ]

5.  Secondary:   Overall Survival   [ Time Frame: Start of randomization (Week 0 of Visit 2) until death (up to a median of 17.1 weeks) ]

6.  Secondary:   Percent Change From Baseline to Week 7 in Peripheral CD5+CD19+ Cell Counts   [ Time Frame: Baseline (Visit 2) until Week 7 (Visit 9) ]

7.  Secondary:   Percent Change From Baseline to Week 7 in Peripheral CD5+CD20+ Cell Counts   [ Time Frame: Baseline (Visit 2) until Week 7 (Visit 9) ]

8.  Secondary:   Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) to Week 24 (Visit 14)   [ Time Frame: Baseline (Visit 2) until Week 24 (Visit 14) ]

9.  Secondary:   Number of Participants With Complete Resolution of Constitutional Symptoms at Week 24   [ Time Frame: Baseline (Visit 2) and Week 24 ]

10.  Secondary:   Number of Participants With Complete Resolution of Lymphadenopathy   [ Time Frame: Baseline (Visit 2) to end of study (up to Week 24) ]

11.  Secondary:   Number of Participants With Improvement on the Eastern Cooperative Oncology Group (ECOG) Performance Status Scale at Week 24   [ Time Frame: Baseline (Visit 2) and Week 24 ]

12.  Secondary:   Number of Participants Who Were Positive, Negative, or Had Missing Data for the Indicated Fluorescence in Situ Hybridization (FISH) Prognostic Factors at Screening   [ Time Frame: Screening (Visit 1, <=14 days prior to Visit 2) ]
  Hide Outcome Measure 12

Measure Type Secondary
Measure Title Number of Participants Who Were Positive, Negative, or Had Missing Data for the Indicated Fluorescence in Situ Hybridization (FISH) Prognostic Factors at Screening
Measure Description The number of participants (par.) who were positive, negative, or had missing data for the following prognostic factors indicative of altered responsiveness to treatment and/or survival was measured: 17p-, 11q-, +12q, 6q-, 13q-. Par. were assessed by FISH for these chromosomal abnormalities known tobe prognostic for time to treatment and survival when detected at diagnosis. Par. were categorized by the chromosomal abnormality detected: 17 p deletion, 11q deletion (but not 17 p deletion), 12 q trisomy (but not 17 p or 111q deletion), 13q deletion only, and no chromosomal abnormalities found.
Time Frame Screening (Visit 1, <=14 days prior to Visit 2)  
Safety Issue No  

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.
FAS. Par. were categorized hierarchically (by severity of abnormality): par. with a 17 p deletion (D); par. with an 11q D, but not a 17 p D; par. with 12q trisomy, but not a 17p or 11q D; par. with no aberrations found; par. with a 13q D as the sole aberration; and par. with 6q D (and not any of the above categories). Some par. had missing data.

Reporting Groups
  Description
2000 mg Ofatumumab + DR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as DR, defined as participants who were enrolled in the study and were refractory to both fludarabine and alemtuzumab.
2000 mg Ofatumumab + BFR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as BFR, defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy.
2000 mg Ofatumumab + Other Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as "other,"defined as participants who were enrolled in the study but did not meet criteria for DR or BFR.

Measured Values
   2000 mg Ofatumumab + DR   2000 mg Ofatumumab + BFR   2000 mg Ofatumumab + Other 
Participants Analyzed 
[Units: Participants]
 92   110   16 
Number of Participants Who Were Positive, Negative, or Had Missing Data for the Indicated Fluorescence in Situ Hybridization (FISH) Prognostic Factors at Screening 
[Units: Participants]
     
FISH 17p-, negative   64   89   14 
FISH 17p-, positive   27   19   1 
FISH 17p-, missing   4   4   1 
FISH 11q-, negative   56   69   11 
FISH 11q-, positive   36   41   5 
FISH 11q-, missing   3   2   0 
FISH +12q, negative   76   91   11 
FISH +12q, positive   15   19   5 
FISH +12q, missing   4   2   0 
FISH 6q-, negative   89   101   15 
FISH 6q-, positive   2   9   0 
FISH 6q-, missing   4   2   1 
FISH 13q-, negative   46   53   9 
FISH 13q-, positive   45   57   7 
FISH 13q-, missing   4   2   0 

No statistical analysis provided for Number of Participants Who Were Positive, Negative, or Had Missing Data for the Indicated Fluorescence in Situ Hybridization (FISH) Prognostic Factors at Screening



13.  Secondary:   Number of Participants With Improvement in Hemoglobin   [ Time Frame: Baseline (Visit 2) to Week 28 ]

14.  Secondary:   Number of Participants With Improvement in Thrombocytopenia (Thromb.)   [ Time Frame: Baseline (Visit 2) to Week 28 ]

15.  Secondary:   Number of Participants With Complete Resolution of Hepatomegaly   [ Time Frame: Baseline (Visit 2) until Week 24 ]

16.  Secondary:   Number of Participants With Improvement in Neutropenia   [ Time Frame: Baseline (Visit 2) to Week 28 ]

17.  Secondary:   Number of Participants With Complete Resolution of Splenomegaly   [ Time Frame: Baseline (Visit 2) until Week 24 ]

18.  Secondary:   Number of Participants Who Experienced Any Adverse Event   [ Time Frame: From first infusion (Visit 2/Week 0) to Visit 21 (Month 24 of follow-up [up to Month 48]) or time of withdrawal (treatment and follow-up) ]

19.  Secondary:   Cmax and Ctrough at Dose 1 (Visit 2, Week 0), Dose 8 (Visit 9, Week 7), and Dose 12 (Visit 14, Week 24)   [ Time Frame: Visit 2 (Week 0), Visit 9 (Week 7), and Visit 14 (Week 24) ]

20.  Secondary:   AUC (0-inf) and AUC(0-tau) at Dose 8 (Visit 9, Week 7) and Dose 12 (Visit 14, Week 24)   [ Time Frame: Visit 9 (Week 7) and Visit 14 (Week 24) ]

21.  Secondary:   Half-life (t1/2) at Dose 8 (Visit 9, Week 7) and at Dose 12 (Visit 14, Week 24)   [ Time Frame: Visit 9 (Week 7) and Visit14 (Week 24) ]

22.  Secondary:   Clearance (CL) After Dose 8 (Visit 9, Week 7) and Dose 12 (Visit 14, Week 24)   [ Time Frame: Visit 9 (Week 7) and Visit 14 (Week 24) ]

23.  Secondary:   Volume of Distribution at Steady State (Vss) at Dose 8 (Visit 9, Week 7) and at Dose 12 (Visit 14, Week 24)   [ Time Frame: Visit 9 (Week 7) and Visit 14 (Week 24) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide 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