Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Antineoplastic Agents

All Drugs and Chemicals

Ofatumumab

Eight once weekly infusions (1 x 300 mg + 7 x 2000 mg), then 2000 mg once monthly for two years

GSK Clinical Trials

The purpose of the trial is to investigate the efficacy and safety of ofatumumab retreatment and maintenance in patients with chronic lymphocytic leukemia who have previously responded or had disease stabilization after ofatumumab in an ongoing trial (Hx-CD20-406).

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

A Single-arm, International, Multi-center Trial Investigating the Efficacy and Safety of Ofatumumab Retreatment and Maintenance in CLL Patients Who Progressed Following Response or Stable Disease After Ofatumumab Treatment in Hx-CD20-406

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.

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.

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 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).

OS is defined as the time from allocation to death.

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.

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.

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.

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.

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.

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.

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.

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.

Genmab

GlaxoSmithKline

SAEs and non-serious AEs were reported for members of the Safety Population, comprised of all participants randomized to treatment who received \>=1 dose of trial medication.

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 + DR

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 + 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 (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).

2000 mg Ofatumumab + Other

Total

Age, Continuous

Sex: Female, Male

Asian

White

Race/Ethnicity, Customized

GSK Response Center

Responders with CR

Responders with nPR

Responders with PR

Non-responders with SD

Non-responders with PD

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.

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

Duration of Response

Progression-Free Survival (PFS)

Time to Next Chronic Lymphocytic Leukemia (CLL) Treatment

Overall Survival (OS)

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.

Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) at Month 4

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.

Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) at Month 12

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.

Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) at Month 24

Screening, Positive, n=15 , 11, 1, 27

Screening, Inconclusive, n = 15 , 11 , 1, 27

Screening, Negative, n = 15 , 11 , 1, 27

Post-ofatumumab, Positive, n = 12 , 8 , 1, 21

Post-ofatumumab, Inconclusive, n=12 , 8, 1, 21

Post-ofatumumab, Negative, n =12 , 8, 1 , 21

This arm includes a total of all three arms combined.

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.

Number of Participants With Negative and Positive Human Anti-human Antibody (HAHA) Results at the Time of Screening and Post Ofatumumab

Number of Participants Who Experienced Any Adverse Event

Number of Participants With the Indicated Major Infections

Number of Participants With Infections Requiring Hospitalization or Intravenous Antibiotics

Cmax Visit 2, n= 16, 11, 1, 28

Cmax Visit 14, n= 8, 5, 0, 13

Ctrough Visit 2, n= 16, 11, 1, 28

Ctrough Visit 14, n= 8, 5, 0, 13

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

Spots Global Cancer Trial Database for Efficacy and Safety of Ofatumumab Retreatment and Maintenance Treatment in Patients With B-cell Chronic Lymphocytic Leukemia (CLL)

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Study Description

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