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Efficacy and Safety of Ofatumumab Retreatment and Maintenance Treatment in Patients With B-cell Chronic Lymphocytic Leukemia (CLL)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Genmab
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00802737
First received: December 4, 2008
Last updated: November 8, 2012
Last verified: November 2012
History of Changes
Results First Received: May 17, 2012  
Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Leukaemia, Lymphocytic, Chronic
Intervention: Drug: Ofatumumab

  Participant Flow
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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 Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 (Study OMB111773; NCT00349349) and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab intravenous (iv) infusion was initiated at 300 milligrams (mg), followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months. These participants were classified as double refractory (DR), defined as participants who were enrolled in Study Hx-CD20-406 and were refractory to both fludarabine and alemtuzumab.
2000 mg Ofatumumab + BFR Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab intravenous (iv) infusion was initiated at 300 milligrams (mg), followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months. These participants were classified 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 Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab intravenous (iv) infusion was initiated at 300 milligrams (mg), followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months. These participants were classified 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     17     11     1  
Ongoing     4     2     0  
COMPLETED     0     0     0  
NOT COMPLETED     17     11     1  
Withdrawn due to Disease Progression                 7                 2                 0  
Death                 6                 5                 1  
Participant Too Unwell                 0                 2                 0  
Ongoing                 4                 2                 0  



  Baseline Characteristics
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Reporting Groups
  Description
2000 mg Ofatumumab + DR Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 (Study OMB111773; NCT00349349) and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab intravenous (iv) infusion was initiated at 300 milligrams (mg), followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months. These participants were classified as double refractory (DR), defined as participants who were enrolled in Study Hx-CD20-406 and were refractory to both fludarabine and alemtuzumab.
2000 mg Ofatumumab + BFR Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab intravenous (iv) infusion was initiated at 300 milligrams (mg), followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months. These participants were classified 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 Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab intravenous (iv) infusion was initiated at 300 milligrams (mg), followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months. These participants were classified 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  
Number of Participants  
[units: participants]
 		  17     11     1     29  
Age  
[units: Years]
Mean ± Standard Deviation 		  64.8  ± 5.83     66.9  ± 9.08     84.0  ± NA [1]   66.3  ± 7.85  
Gender  
[units: Participants]
 		       
Female     4     4     1     9  
Male     13     7     0     20  
Race/Ethnicity, Customized  
[units: participants]
 		       
Asian     1     0     0     1  
White     16     11     1     28  
[1] A standard deviation of the mean was not calculated for one participant.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants (Par.) Classified as Responders (Rs) and Non-responders (NRs) for Objective Response in Accordance With the National Cancer Institute Working Group (NCIWG) 1996 Guidelines   [ Time Frame: Start of treatment (Week 0/Visit 2) until Week 52 ]
  Show Outcome Measure 1

2.  Secondary:   Duration of Response   [ Time Frame: Start of treatment (Week 0 of Visit 2) until Week 52 ]
  Show Outcome Measure 2

3.  Secondary:   Progression-Free Survival (PFS)   [ Time Frame: Start of treatment (Week 0 of Visit 2) until Week 52 ]
  Hide Outcome Measure 3

Measure Type Secondary
Measure Title Progression-Free Survival (PFS)
Measure Description PFS is defined as the time from randomization until progression (prog.)/death. Prog. events are defined by well-documented and verifiable data; other data are censored. If the par. had prog. between scheduled visits, died before the first assessment, or died between adequate visits, the endpoint was considered progressed. If there was no prog. at the end of the trial, treatment discontinuation for undocumented prog./toxicity/other reason, new anti-cancer treatment, and death/prog. after >=2 missed visits in a row, the endpoint was censored. Clinical prog. is not considered as a prog. endpoint.
Time Frame Start of treatment (Week 0 of Visit 2) until Week 52  
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

Reporting Groups
  Description
2000 mg Ofatumumab + DR Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 (Study OMB111773; NCT00349349) and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab intravenous (iv) infusion was initiated at 300 milligrams (mg), followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months. These participants were classified as double refractory (DR), defined as participants who were enrolled in Study Hx-CD20-406 and were refractory to both fludarabine and alemtuzumab.
2000 mg Ofatumumab + BFR Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab intravenous (iv) infusion was initiated at 300 milligrams (mg), followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months. These participants were classified 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 Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab intravenous (iv) infusion was initiated at 300 milligrams (mg), followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months. These participants were classified 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  
Number of Participants Analyzed  
[units: participants]
 		  17     11     1  
Progression-Free Survival (PFS)  
[units: months]
Median ( 95% Confidence Interval ) 		  7.9  
  ( 3.4 to 12.9 )   		  7.2  
  ( 2.0 to 11.6 )   		  NA  
  ( NA to NA ) [1]
[1] There were not enough events on the survival curve to estimate a median or confidence interval.

No statistical analysis provided for Progression-Free Survival (PFS)



4.  Secondary:   Time to Next Chronic Lymphocytic Leukemia (CLL) Treatment   [ Time Frame: Time from start of study treatment (Week 0 of Visit 2) until the time of first administration of a CLL treatment other than ofatumumab (assessed for a mean of 11.4 months) ]
  Show Outcome Measure 4

5.  Secondary:   Overall Survival (OS)   [ Time Frame: Time from start of study treatment (Week 0 of Visit 2) until date of death or time that participant was no longer followed (median of 18.0 months) ]
  Show Outcome Measure 5

6.  Secondary:   Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) at Week 24   [ Time Frame: Baseline (Visit 2) and Week 24 ]
  Show Outcome Measure 6

7.  Secondary:   Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) at Week 52   [ Time Frame: Baseline (Visit 2) and Week 52 ]
  Show Outcome Measure 7

8.  Secondary:   Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) at Week 104   [ Time Frame: Baseline (Visit 2) and Week 104 ]
  Show Outcome Measure 8

9.  Secondary:   Number of Participants With Negative and Positive Human Anti-human Antibody (HAHA) Results at the Time of the Last Visit (up to Month 26)   [ Time Frame: Time of last visit (up to Month 26) ]
  Show Outcome Measure 9

10.  Secondary:   Number of Participants Who Experienced Any Adverse Event   [ Time Frame: From the first infusion (Visit 2/Week 0) up to Visit 34 (Month 3 of follow-up [up to Month 26]) or time of withdrawal (treatment and follow-up) ]
  Show Outcome Measure 10

11.  Secondary:   Number of Participants With the Indicated Major Infections   [ Time Frame: From the first infusion (Visit 2/Week 0) up to Visit 34 (Month 3 of follow-up [up to Month 26]) or time of withdrawal (treatment and follow-up) ]
  Show Outcome Measure 11

12.  Secondary:   Number of Participants With Infections Requiring Hospitalization or Intravenous Antibiotics   [ Time Frame: From the first infusion (Visit 2/Week 0) up to Visit 34 (Month 3 of follow-up [up to Month 26]) or time of withdrawal (treatment and follow-up) ]
  Show Outcome Measure 12

13.  Secondary:   Cmax and Ctrough at Dose 1 (Visit 2, Week 0), Dose 5 (Visit 6, Week 4), and at Every Second Dose From Dose 10 (Visit 12, Month 4) Through Dose 32 (Visit 34, Month 26)   [ Time Frame: Visit 2 (Week 0), Visit 6 (Week 4); every second visit starting at Visit 12 (Month 4) until Visit 34 (Month 26). In all visits, two samples for PK were collected, one prior to start of infusion and one at the end of infusion. ]
Results not yet posted.   Anticipated Posting Date:   07/2012   Safety Issue:   No


  Serious Adverse Events
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  Other Adverse Events
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  More Information
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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.


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.  


Results Point of Contact:  
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343


No publications provided


Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00802737     History of Changes
Other Study ID Numbers: 111827, GEN416
Study First Received: December 4, 2008
Results First Received: May 17, 2012
Last Updated: November 8, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Germany: Paul-Ehrlich-Institut
Sweden: Medical Products Agency
United States: Food and Drug Administration
Czech Republic: State Institute for Drug Control