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

This study has been completed.
Sponsor:
Collaborator:
Genmab
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00802737
First received: December 4, 2008
Last updated: April 24, 2014
Last verified: April 2014
  Purpose

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).


Condition Intervention Phase
Leukaemia, Lymphocytic, Chronic
Drug: Ofatumumab
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Duration of Response [ Time Frame: From the time of the initial response until progression or death (average of 14.1 study months) ] [ Designated as safety issue: No ]
    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.

  • Progression-Free Survival (PFS) [ Time Frame: Start of treatment (Week 0 of Visit 2) until progression or death (average of 14.1 study months) ] [ Designated as safety issue: No ]
    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 [ 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 (average of 14.8 study months) ] [ Designated as safety issue: No ]
    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).

  • 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) ] [ Designated as safety issue: No ]
    OS is defined as the time from allocation to death.

  • Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) at Month 4 [ Time Frame: Baseline (Visit 2) and Month 4 ] [ Designated as safety issue: No ]
    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.

  • Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) at Month 12 [ Time Frame: Baseline (Visit 2) and Month 12 ] [ Designated as safety issue: No ]
    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.

  • Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) at Month 24 [ Time Frame: Baseline (Visit 2) and Month 24 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Negative and Positive Human Anti-human Antibody (HAHA) Results at the Time of Screening and Post Ofatumumab [ Time Frame: Screening and post ofatumumab (up to Study Month 32) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Who Experienced Any Adverse Event [ Time Frame: 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]) ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With the Indicated Major Infections [ Time Frame: 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]) ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Infections Requiring Hospitalization or Intravenous Antibiotics [ Time Frame: 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]) ] [ Designated as safety issue: Yes ]
    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 and Ctrough at Visit 2 (Week 0) and at Visit 14 (Month 4) [ Time Frame: Visit 2 (Week 0) and Visit 14 (Month 4) ] [ Designated as safety issue: No ]
    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.


Enrollment: 29
Study Start Date: January 2009
Study Completion Date: May 2013
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ofatumumab
Eight once weekly infusions (1 x 300 mg + 7 x 2000 mg), then 2000 mg once monthly for two years
Drug: Ofatumumab
Eight once weekly infusions (1 x 300 mg + 7 x 2000 mg), then 2000 mg once monthly for two years
Other Name: HuMax-CD20

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has responded to ofatumumab treatment (CR, nPR, PR) or has had SD at least up to and including visit number 14 (24 weeks after first infusion) in the Hx-CD20-406 trial.
  • Has disease progression after visit number 14 (24 weeks after first infusion) in the Hx CD20 406 trial.
  • Received at least eight ofatumumab infusions.
  • Has active CLL with an indication for treatment.
  • Has Eastern Cooperative Oncology Group (ECOG) performance status grade 0, 1 or 2.
  • Provides signed informed consent, following receipt of verbal and written information about the trial, before any trial related activity is carried out.
  • If previously treated in GEN416 (this trial), the patient must have achieved CR with subsequent disease progression 24 weeks or later after the first infusion in the GEN416 trial.

Exclusion Criteria:

  • The disease has transformed to more aggressive B-cell malignancies (e.g. diffuse large B-cell lymphoma, Richter's syndrome or prolymphocytic leukemia).
  • Has a suspected treatment requiring malignancy other than CLL.
  • Has received treatment other than ofatumumab within two weeks prior to visit 2.
  • Has clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months from visit 1, congestive heart failure (NYHA III IV), and arrhythmia requiring therapy, with the exception of clinically non-significant extra systoles or minor conduction abnormalities.
  • Has significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease.
  • Has a history of significant cerebrovascular disease.
  • Is known HIV positive.
  • Has positive serology for hepatitis B, defined as a positive test for HBsAg and/or positive tests for both anti-HBs and anti-HBc.
  • Has known or suspected hypersensitivity to components of the IMP.
  • Has received treatment with any non-marketed drug substance or experimental therapy other than ofatumumab within four weeks prior to visit 2.
  • Currently participates in any other interventional clinical trial other than Hx-CD20-406.
  • Known or suspected to not being able to comply with a trial protocol (e.g. due to alcoholism, drug dependency or psychiatric disorder).
  • Is breast feeding (women only).
  • Has a positive pregnancy test at screening (women only).
  • Is not willing to use adequate contraception during the trial and one year after last dose of ofatumumab (women only). Adequate contraception is defined as hormonal birth control or intrauterine device. For patients in the US the use of double barrier method is considered adequate.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00802737

Locations
Sweden
GSK Investigational Site
Stockholm, Sweden, SE-171 76
GSK Investigational Site
Örebro, Sweden, SE-701 85
Sponsors and Collaborators
GlaxoSmithKline
Genmab
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

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: April 24, 2014
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

Keywords provided by GlaxoSmithKline:
Maintenance
Retreatment
Chronic lymphocytic leukemia
B-Cell Chronic Lymphocytic Leukemia
Ofatumumab

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell

ClinicalTrials.gov processed this record on October 01, 2014