Trial Outcomes & Findings for Efficacy and Safety of Ofatumumab Retreatment and Maintenance Treatment in Patients With B-cell Chronic Lymphocytic Leukemia (CLL) (NCT NCT00802737)

Last Updated: 2014-05-14

Results Overview

Par. with complete remission (CR), nodular partial remission (nPR), and partial remission (PR) on 2 consecutive visits \>=56 days apart were classified as Rs; those with stable disease (SD)/progressive disease (PD) were classified as NRs. Per the NCIWG 1996 guidelines: CR; no lymphadenopathy/hepatomegaly/splenomegaly/constitutional symptoms, normal hematology, normocellular bone marrow sample for age, \<30% lymphocytes (LC), no lymphoid nodule; PR: \>=50% decrease in LC/lymphadenopathy; nPR: persistent bone marrow nodules; PD: new lesion or increase by \>=50% from baseline; SD: no CR, PR, or PD.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

29 participants

Primary outcome timeframe

Start of treatment (Week 0/Visit 2) until Week 52

Results posted on

2014-05-14

Participant Flow

Per study protocol

Completed study Hx-CD20-406 (Study OMB111773; NCT00349349)

Participant milestones

Participant milestones
Measure	2000 mg Ofatumumab + DR Participants (Par.) 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 after which, if possible, the par. entered the Follow-up phase (Months 29-44). 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. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	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 iv infusion was initiated at 300 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 after which, if possible, the par. entered the Follow-up phase (Months 29-44). 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. Par. with disease progression entered into the Extended Follow-up phase (Months 47 to 62).	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 iv infusion was initiated at 300 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 after which, if possible, the par. entered the Follow-up (Months 29-44). These participants were classified as "other," defined as participants who were enrolled in the study but did not meet criteria for DR or BFR. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).
Overall Study STARTED	17	11	1
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	17	11	1

Reasons for withdrawal

Reasons for withdrawal
Measure	2000 mg Ofatumumab + DR Participants (Par.) 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 after which, if possible, the par. entered the Follow-up phase (Months 29-44). 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. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	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 iv infusion was initiated at 300 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 after which, if possible, the par. entered the Follow-up phase (Months 29-44). 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. Par. with disease progression entered into the Extended Follow-up phase (Months 47 to 62).	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 iv infusion was initiated at 300 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 after which, if possible, the par. entered the Follow-up (Months 29-44). These participants were classified as "other," defined as participants who were enrolled in the study but did not meet criteria for DR or BFR. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).
Overall Study Withdrawn due to Disease Progression	9	3	0
Overall Study Death	6	5	1
Overall Study Adverse Event	1	0	0
Overall Study Received Prohibited Therapy	1	0	0
Overall Study Ongoing CLL-Treatment	0	1	0
Overall Study Participant too Unwell	0	2	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	2000 mg Ofatumumab + DR n=17 Participants Participants (Par.) 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 after which, if possible, the par. entered the Follow-up phase (Months 29-44). 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. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	2000 mg Ofatumumab + BFR n=11 Participants 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 iv infusion was initiated at 300 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 after which, if possible, the par. entered the Follow-up phase (Months 29-44). 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. Par. with disease progression entered into the Extended Follow-up phase (Months 47 to 62).	2000 mg Ofatumumab + Other n=1 Participants 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 iv infusion was initiated at 300 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 after which, if possible, the par. entered the Follow-up (Months 29-44). These participants were classified as "other," defined as participants who were enrolled in the study but did not meet criteria for DR or BFR. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	Total n=29 Participants Total of all reporting groups
Age, Continuous	64.8 Years STANDARD_DEVIATION 5.83 • n=5 Participants	66.9 Years STANDARD_DEVIATION 9.08 • n=7 Participants	84.0 Years STANDARD_DEVIATION NA • n=5 Participants	66.3 Years STANDARD_DEVIATION 7.85 • n=4 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	9 Participants n=4 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	7 Participants n=7 Participants	0 Participants n=5 Participants	20 Participants n=4 Participants
Race/Ethnicity, Customized Asian	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Race/Ethnicity, Customized White	16 participants n=5 Participants	11 participants n=7 Participants	1 participants n=5 Participants	28 participants n=4 Participants

PRIMARY outcome

Timeframe: Start of treatment (Week 0/Visit 2) until Week 52

Population: Full Analysis Set (FAS): all participants who had been exposed to study drug irrespective of their compliance to the planned course of treatment. Some participants were not evaluable (NE) due to participant withdraw, refusal, non-trial drug-related adverse events, and death.

Outcome measures

Outcome measures
Measure	2000 mg Ofatumumab + DR n=17 Participants Participants (Par.) 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 after which, if possible, the par. entered the Follow-up phase (Months 29-44). 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. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	2000 mg Ofatumumab + BFR n=11 Participants 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 iv infusion was initiated at 300 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 after which, if possible, the par. entered the Follow-up phase (Months 29-44). 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. Par. with disease progression entered into the Extended Follow-up phase (Months 47 to 62).	2000 mg Ofatumumab + Other n=1 Participants 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 iv infusion was initiated at 300 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 after which, if possible, the par. entered the Follow-up (Months 29-44). These participants were classified as "other," defined as participants who were enrolled in the study but did not meet criteria for DR or BFR. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	Total This arm includes a total of all three arms combined.
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 Responders with CR	2 participants	0 participants	0 participants	—
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 Responders with nPR	0 participants	0 participants	0 participants	—
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 Responders with PR	2 participants	2 participants	1 participants	—
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 Non-responders with SD	8 participants	7 participants	0 participants	—
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 Non-responders with PD	3 participants	0 participants	0 participants	—
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 NE	2 participants	2 participants	0 participants	—

SECONDARY outcome

Timeframe: From the time of the initial response until progression or death (average of 14.1 study months)

Population: FAS

Duration of response is defined as the time from the initial response (first visit at which response is observed) to progression or death. If the participant had progression between scheduled visits, no progression at the end of the trial, treatment discontinuation for undocumented progression, treatment discontinuation for toxicity or other reason, new anti-cancer treatment, and experienced death or progression after two or more missed visits in a row the endpoint was censored.

Outcome measures

Outcome measures
Measure	2000 mg Ofatumumab + DR n=17 Participants Participants (Par.) 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 after which, if possible, the par. entered the Follow-up phase (Months 29-44). 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. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	2000 mg Ofatumumab + BFR n=11 Participants 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 iv infusion was initiated at 300 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 after which, if possible, the par. entered the Follow-up phase (Months 29-44). 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. Par. with disease progression entered into the Extended Follow-up phase (Months 47 to 62).	2000 mg Ofatumumab + Other n=1 Participants 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 iv infusion was initiated at 300 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 after which, if possible, the par. entered the Follow-up (Months 29-44). These participants were classified as "other," defined as participants who were enrolled in the study but did not meet criteria for DR or BFR. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	Total This arm includes a total of all three arms combined.
Duration of Response	NA months Interval 7.2 to There were not enough events on the survival curve to estimate a median or upper limit of confidence interval.	NA months Interval 24.1 to There were not enough events on the survival curve to estimate a median or upper limit of confidence interval	NA months There were not enough events on the survival curve to estimate a median or confidence interval.	—

SECONDARY outcome

Timeframe: Start of treatment (Week 0 of Visit 2) until progression or death (average of 14.1 study months)

Population: FAS

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.

Outcome measures

Outcome measures
Measure	2000 mg Ofatumumab + DR n=17 Participants Participants (Par.) 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 after which, if possible, the par. entered the Follow-up phase (Months 29-44). 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. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	2000 mg Ofatumumab + BFR n=11 Participants 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 iv infusion was initiated at 300 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 after which, if possible, the par. entered the Follow-up phase (Months 29-44). 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. Par. with disease progression entered into the Extended Follow-up phase (Months 47 to 62).	2000 mg Ofatumumab + Other n=1 Participants 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 iv infusion was initiated at 300 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 after which, if possible, the par. entered the Follow-up (Months 29-44). These participants were classified as "other," defined as participants who were enrolled in the study but did not meet criteria for DR or BFR. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	Total This arm includes a total of all three arms combined.
Progression-Free Survival (PFS)	7.9 months Interval 3.2 to 12.9	7.2 months Interval 2.0 to 11.6	NA months There were not enough events on the survival curve to estimate a median or confidence interval.	—

SECONDARY outcome

Timeframe: Time from start of study treatment (Week 0 of Visit 2) until the time of first administration of a CLL treatment other than ofatumumab (average of 14.8 study months)

Population: FAS

Time to next chronic lymphocytic leukemia (CLL) treatment is defined as the time from treatment allocation/randomization (Visit 2) until the time of the first administration of the next CLL treatment other than ofatumumab (or HuMaxCD20, a fully human monoclonal antibody to CD20 that is expressed on the surface of B-cells).

Outcome measures

Outcome measures
Measure	2000 mg Ofatumumab + DR n=17 Participants Participants (Par.) 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 after which, if possible, the par. entered the Follow-up phase (Months 29-44). 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. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	2000 mg Ofatumumab + BFR n=11 Participants 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 iv infusion was initiated at 300 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 after which, if possible, the par. entered the Follow-up phase (Months 29-44). 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. Par. with disease progression entered into the Extended Follow-up phase (Months 47 to 62).	2000 mg Ofatumumab + Other n=1 Participants 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 iv infusion was initiated at 300 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 after which, if possible, the par. entered the Follow-up (Months 29-44). These participants were classified as "other," defined as participants who were enrolled in the study but did not meet criteria for DR or BFR. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	Total This arm includes a total of all three arms combined.
Time to Next Chronic Lymphocytic Leukemia (CLL) Treatment	13.9 months Interval 3.9 to There were not enough events on the survival curve to estimate the upper limit of the confidence interval.	11.6 months Interval 7.0 to There were not enough events on the survival curve to estimate the upper limit of the confidence interval.	NA months There were not enough events on the survival curve to estimate a median or confidence interval.	—

SECONDARY outcome

Timeframe: 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)

Population: FAS

OS is defined as the time from allocation to death.

Outcome measures

Outcome measures
Measure	2000 mg Ofatumumab + DR n=17 Participants Participants (Par.) 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 after which, if possible, the par. entered the Follow-up phase (Months 29-44). 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. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	2000 mg Ofatumumab + BFR n=11 Participants 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 iv infusion was initiated at 300 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 after which, if possible, the par. entered the Follow-up phase (Months 29-44). 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. Par. with disease progression entered into the Extended Follow-up phase (Months 47 to 62).	2000 mg Ofatumumab + Other n=1 Participants 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 iv infusion was initiated at 300 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 after which, if possible, the par. entered the Follow-up (Months 29-44). These participants were classified as "other," defined as participants who were enrolled in the study but did not meet criteria for DR or BFR. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	Total This arm includes a total of all three arms combined.
Overall Survival (OS)	27.6 months Interval 5.4 to There were not enough events on the survival curve to estimate the upper limit of the confidence interval.	11.3 months Interval 5.3 to There were not enough events on the survival curve to estimate the upper limit of the confidence interval.	12.3 months There were not enough events on the survival curve to estimate a confidence interval.	—

SECONDARY outcome

Timeframe: Baseline (Visit 2) and Month 4

Population: FAS. Measurement of tumor size was completed by physical examination for participants remaining in the study at Month 4. Only participants with a baseline value and a post-baseline value at Month 4 were included in the calculation.

Reduction in tumor size was measured as the percent change in the sum of the products of the diameters of the largest abnormal lymph nodes from Baseline to Week 24. Percent change was calculated as (Week 24 SPD minus Baseline SPD)/Baseline SPD \* 100.

Outcome measures

Outcome measures
Measure	2000 mg Ofatumumab + DR n=8 Participants Participants (Par.) 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 after which, if possible, the par. entered the Follow-up phase (Months 29-44). 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. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	2000 mg Ofatumumab + BFR n=6 Participants 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 iv infusion was initiated at 300 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 after which, if possible, the par. entered the Follow-up phase (Months 29-44). 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. Par. with disease progression entered into the Extended Follow-up phase (Months 47 to 62).	2000 mg Ofatumumab + Other n=1 Participants 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 iv infusion was initiated at 300 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 after which, if possible, the par. entered the Follow-up (Months 29-44). These participants were classified as "other," defined as participants who were enrolled in the study but did not meet criteria for DR or BFR. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	Total This arm includes a total of all three arms combined.
Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) at Month 4	-55.3 Percent change in tumor size Interval -100.0 to 157.0	-64.8 Percent change in tumor size Interval -82.0 to 3.0	0 Percent change in tumor size Interval 0.0 to 0.0	—

SECONDARY outcome

Timeframe: Baseline (Visit 2) and Month 12

Population: FAS. No participants in the 2000 mg Ofatumumab + Other treatment arm were able to contribute to this measure. Measurement of tumor size was completed by physical examination for participants remaining in the study at Month 12. Only participants with a baseline value and a post-baseline value at Month 12 were included in the calculation.

Reduction in tumor size was measured by the percentage change in the sum of products of the diameters of the largest abnormal lymph nodes from Baseline to Month 12. Percent change was calculated as (Month 12 SPD minus Baseline SPD)/Baseline SPD \* 100.

Outcome measures

Outcome measures
Measure	2000 mg Ofatumumab + DR n=4 Participants Participants (Par.) 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 after which, if possible, the par. entered the Follow-up phase (Months 29-44). 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. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	2000 mg Ofatumumab + BFR n=1 Participants 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 iv infusion was initiated at 300 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 after which, if possible, the par. entered the Follow-up phase (Months 29-44). 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. Par. with disease progression entered into the Extended Follow-up phase (Months 47 to 62).	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 iv infusion was initiated at 300 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 after which, if possible, the par. entered the Follow-up (Months 29-44). These participants were classified as "other," defined as participants who were enrolled in the study but did not meet criteria for DR or BFR. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	Total This arm includes a total of all three arms combined.
Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) at Month 12	-65.2 Percent change in tumor size Interval -100.0 to 0.0	-68.9 Percent change in tumor size Interval -68.9 to -68.9	—	—

SECONDARY outcome

Timeframe: Baseline (Visit 2) and Month 24

Population: FAS. No participants in the 2000 mg Ofatumumab + Other treatment arm were able to contribute to this measure. Measurement of tumor size was completed by physical examination for participants remaining in the study at Month 24. Only participants with a baseline value and a post-baseline value at Month 24 were included in the calculation.

Reduction in tumor size was measured by the percentage change in the sum of products of the diameters of the largest abnormal lymph nodes from Baseline to Month 24. Percent change was calculated as (Month 24 SPD minus Baseline SPD)/Baseline SPD \* 100.

Outcome measures

Outcome measures
Measure	2000 mg Ofatumumab + DR n=2 Participants Participants (Par.) 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 after which, if possible, the par. entered the Follow-up phase (Months 29-44). 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. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	2000 mg Ofatumumab + BFR n=1 Participants 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 iv infusion was initiated at 300 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 after which, if possible, the par. entered the Follow-up phase (Months 29-44). 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. Par. with disease progression entered into the Extended Follow-up phase (Months 47 to 62).	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 iv infusion was initiated at 300 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 after which, if possible, the par. entered the Follow-up (Months 29-44). These participants were classified as "other," defined as participants who were enrolled in the study but did not meet criteria for DR or BFR. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	Total This arm includes a total of all three arms combined.
Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) at Month 24	-83.3 Percent change in tumor size Interval -100.0 to -67.0	-64.0 Percent change in tumor size Interval -64.0 to -64.0	—	—

SECONDARY outcome

Timeframe: Screening and post ofatumumab (up to Study Month 32)

Population: FAS. During the study, samples were to be taken at the last visit; however, this may not have been possible, such as in cases of death, or when the visit was not obvious as the "last visit." Therefore, some samples were not available or were not collected.

HAHAs are indicators of immunogenicity to ofatumumab. HAHA levels were assessed for each participant at the end of participation in the study (at their last visit). A positive HAHA status indicates a positive enzyme-linked immunosorbent assay (ELISA) result, an inconclusive status indicates a negative ELISA result at ofatumumab concentration above the threshold at which ofatumumab may interfere with the assay, and a negative status indicates a negative ELISA result at ofatumumab concentration below the threshold.

Outcome measures

Outcome measures
Measure	2000 mg Ofatumumab + DR n=17 Participants Participants (Par.) 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 after which, if possible, the par. entered the Follow-up phase (Months 29-44). 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. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	2000 mg Ofatumumab + BFR n=11 Participants 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 iv infusion was initiated at 300 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 after which, if possible, the par. entered the Follow-up phase (Months 29-44). 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. Par. with disease progression entered into the Extended Follow-up phase (Months 47 to 62).	2000 mg Ofatumumab + Other n=1 Participants 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 iv infusion was initiated at 300 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 after which, if possible, the par. entered the Follow-up (Months 29-44). These participants were classified as "other," defined as participants who were enrolled in the study but did not meet criteria for DR or BFR. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	Total n=29 Participants This arm includes a total of all three arms combined.
Number of Participants With Negative and Positive Human Anti-human Antibody (HAHA) Results at the Time of Screening and Post Ofatumumab Screening, Positive, n=15 , 11, 1, 27	0 participants	0 participants	0 participants	0 participants
Number of Participants With Negative and Positive Human Anti-human Antibody (HAHA) Results at the Time of Screening and Post Ofatumumab Screening, Inconclusive, n = 15 , 11 , 1, 27	5 participants	6 participants	0 participants	11 participants
Number of Participants With Negative and Positive Human Anti-human Antibody (HAHA) Results at the Time of Screening and Post Ofatumumab Screening, Negative, n = 15 , 11 , 1, 27	10 participants	5 participants	1 participants	16 participants
Number of Participants With Negative and Positive Human Anti-human Antibody (HAHA) Results at the Time of Screening and Post Ofatumumab Post-ofatumumab, Positive, n = 12 , 8 , 1, 21	0 participants	0 participants	0 participants	0 participants
Number of Participants With Negative and Positive Human Anti-human Antibody (HAHA) Results at the Time of Screening and Post Ofatumumab Post-ofatumumab, Inconclusive, n=12 , 8, 1, 21	9 participants	8 participants	1 participants	18 participants
Number of Participants With Negative and Positive Human Anti-human Antibody (HAHA) Results at the Time of Screening and Post Ofatumumab Post-ofatumumab, Negative, n =12 , 8, 1 , 21	3 participants	0 participants	0 participants	3 participants

SECONDARY outcome

Timeframe: From the first infusion (Visit 2/Week 0) until the last visit of the Extended Follow-up Phase (up to Study Month 26 [visit 34])

Population: FAS

An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with the treatment. A list of AEs experienced in the study with a frequency threshold of 5% can be found in the AE section of this results record.

Outcome measures

Outcome measures
Measure	2000 mg Ofatumumab + DR n=17 Participants Participants (Par.) 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 after which, if possible, the par. entered the Follow-up phase (Months 29-44). 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. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	2000 mg Ofatumumab + BFR n=11 Participants 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 iv infusion was initiated at 300 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 after which, if possible, the par. entered the Follow-up phase (Months 29-44). 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. Par. with disease progression entered into the Extended Follow-up phase (Months 47 to 62).	2000 mg Ofatumumab + Other n=1 Participants 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 iv infusion was initiated at 300 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 after which, if possible, the par. entered the Follow-up (Months 29-44). These participants were classified as "other," defined as participants who were enrolled in the study but did not meet criteria for DR or BFR. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	Total This arm includes a total of all three arms combined.
Number of Participants Who Experienced Any Adverse Event	15 participants	11 participants	1 participants	—

SECONDARY outcome

Timeframe: From the first infusion (Visit 2/Week 0) until the last visit of the Extended Follow-up Phase (up to Study Month 26 [visit 34])

Population: FAS

The data collected for this analysis are reported in the overall Serious Adverse Events (SAEs) of infections rather than reported separately for this specific analysis. This is a conservative approach for reporting all infectious SAEs in order to ensure that all of the infectious SAEs are represented.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From the first infusion (Visit 2/Week 0) until the last visit of the Extended Follow-up Phase (up to Study Month 26 [visit 34])

Population: FAS

The data collected for this analysis are reported in the overall SAEs of infections rather than reported separately for this specific analysis. This is a conservative approach for reporting all infectious SAEs in order to ensure that all of the infectious SAEs are represented.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Visit 2 (Week 0) and Visit 14 (Month 4)

Population: FAS. Data are provided for the number of participants attending each visit. Participants withdrawn during the study were not analyzed.

Cmax is defined as the maximum concentration of drug in plasma samples (collected at the end of the infusion). Ctrough is defined as the concentration of drug in plasma samples at the end of a dosing interval (collected directly before next administration). Ctrough before the first infusion represents residual ofatumumab from participation in Study Hx-CD20-406.

Outcome measures

Outcome measures
Measure	2000 mg Ofatumumab + DR n=17 Participants Participants (Par.) 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 after which, if possible, the par. entered the Follow-up phase (Months 29-44). 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. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	2000 mg Ofatumumab + BFR n=11 Participants 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 iv infusion was initiated at 300 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 after which, if possible, the par. entered the Follow-up phase (Months 29-44). 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. Par. with disease progression entered into the Extended Follow-up phase (Months 47 to 62).	2000 mg Ofatumumab + Other n=1 Participants 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 iv infusion was initiated at 300 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 after which, if possible, the par. entered the Follow-up (Months 29-44). These participants were classified as "other," defined as participants who were enrolled in the study but did not meet criteria for DR or BFR. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	Total n=29 Participants This arm includes a total of all three arms combined.
Cmax and Ctrough at Visit 2 (Week 0) and at Visit 14 (Month 4) Cmax Visit 2, n= 16, 11, 1, 28	54.8 Milligrams per liter (mg/L) Interval 30.7 to 97.7	58.8 Milligrams per liter (mg/L) Interval 38.6 to 89.5	110 Milligrams per liter (mg/L) The 95% CI could not be calculated due to the sample size (n=1).	57.7 Milligrams per liter (mg/L) Interval 40.7 to 82.0
Cmax and Ctrough at Visit 2 (Week 0) and at Visit 14 (Month 4) Cmax Visit 14, n= 8, 5, 0, 13	617 Milligrams per liter (mg/L) Interval 413.0 to 922.0	708 Milligrams per liter (mg/L) Interval 352.0 to 1424.0	NA Milligrams per liter (mg/L) Participants in group Ofatumumab + Other did not have a sample collection at Visit 14.	651 Milligrams per liter (mg/L) Interval 482.0 to 877.0
Cmax and Ctrough at Visit 2 (Week 0) and at Visit 14 (Month 4) Ctrough Visit 2, n= 16, 11, 1, 28	1.1 Milligrams per liter (mg/L) Interval 0.32 to 4.0	2.8 Milligrams per liter (mg/L) Interval 1.1 to 7.5	0.0 Milligrams per liter (mg/L) The 95% CI could not be calculated due to the sample size (n=1).	1.7 Milligrams per liter (mg/L) Interval 0.77 to 3.6
Cmax and Ctrough at Visit 2 (Week 0) and at Visit 14 (Month 4) Ctrough Visit 14, n= 8, 5, 0, 13	42.6 Milligrams per liter (mg/L) Interval 6.4 to 285.0	59.5 Milligrams per liter (mg/L) Interval 4.7 to 757.0	NA Milligrams per liter (mg/L) Participants in group Ofatumumab + Other did not have a sample collection at Visit 14.	48.5 Milligrams per liter (mg/L) Interval 13.6 to 173.0

Adverse Events

2000 mg Ofatumumab + DR

Serious events: 11 serious events

Other events: 15 other events

Deaths: 0 deaths

2000 mg Ofatumumab + BFR

Serious events: 10 serious events

Other events: 11 other events

Deaths: 0 deaths

2000 mg Ofatumumab + Other

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER