HuMax-CD20 i(Ofatumumab) n Follicular Lymphoma (FL) Patients Refractory to Rituximab
This study has been completed.
Information provided by (Responsible Party):
First received: October 31, 2006
Last updated: December 12, 2013
Last verified: November 2013
A Single-Arm, International, Multi-Center Trial of HuMax-CD20 (Ofatumumab), a Fully Human Monoclonal Anti-CD20 Antibody, in Patients With Follicular Lymphoma Who Are Refractory to Rituximab as Monotherapy or in Combination With Chemotherapy
|Study Design:||Intervention Model: Single Group Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Single-arm, International, Multi-center Trial of HuMax-CD20, a Fully Human Monoclonal Anti-CD20 Antibody, in Patients With Follicular Lymphoma Who Are Refractory to Rituximab as Monotherapy or in Combination With Chemotherapy|
Resource links provided by NLM:
U.S. FDA Resources
Further study details as provided by GlaxoSmithKline:
Primary Outcome Measures:
- Number of Participants With Objective Response (OR) [ Time Frame: Start of treatment (Day 1 of Week 0) until 3 months after start of last infusion (up to Week 32) ]OR was assessed by an Independent endpoints Review Committee (IRC) according to the standardized response criteria for Non-Hodgkin's lymphoma. Participants with Complete Response (CR; complete disappearance of all detectable disease), Complete Response unconfirmed (CRu; any residual lymph node/nodal mass >1.5 centimeters [cm] in its longest transverse diameter that regressed >75% compared to baseline), or Partial Response (PR; >=50% decrease in the sum of the product of diameters of indicator lesions) were defined as responders for OR.
- Number of Participants Classified as Responders and Non-responders for Objective Response (OR) [ Time Frame: 6-month period from the start of treatment. There was a median time of response at Month 5.5 (participants were followed for up to 24 months). ]Based on OR over a 6-month period from start of treatment, participants were classified as responders/non-responders as follows: participants with CR, CRu, or PR were classified as responders, whereas participants with Stable Disease (SD; achieving less than PR but not consistent with PD), Progressive Disease (PD; 50% increase from nadir in the products of the greatest perpendicular diameters of any previously identified node or appearance of any new node >1 cm), or Not Evaluable (NE) participants were classified as non-responders.
Secondary Outcome Measures:
- Duration of Response [ Time Frame: From start of treatment (Week 0) until Month 24 ]The duration of response is defined as the time from the initial response (the first visit at which response was observed) to progression or death. For participants who were lost to follow-up, duration of response was censored at the date of the last attended visit at which the endpoint was assessed. The Kaplan-Meier method was used to estimate duration of response.
- Progression-Free Survival [ Time Frame: From start of treatment (Week 0) until Month 24 ]Progression-free survival (PFS) is defined as the time from randomization until the first radiologically or clinically documented evidence of progression or death due to any cause, if sooner. For participants who were lost to follow-up, PFS was censored at the date of the last attended visit at which the endpoint was assessed. The Kaplan-Meier method was used to estimate PFS.
- Time to Next Follicular Lymphoma (FL) Therapy [ Time Frame: From start of treatment (Week 0) until Month 24 ]Time to next FL (anti-lymphoma) therapy is defined as the time from randomization until the time of first administration of the next anti-lymphoma therapy other than ofatumumab. For participants who were lost to follow-up, the time was censored at the date of the last attended visit at which the endpoint was assessed.
- Overall Survival [ Time Frame: First dose (Week 0) until 5 years ]Overall survival is defined as the time from randomization until death. For participants who are lost to follow-up, overall survival will be censored at the date of the last attended visit at which the endpoint was assessed.
- Percent Change From Screening (Visit 1) in Tumor Size as Assessed by Radiologist 1 (R1) and Radiologist 2 (R2) at Months 3, 6, 9, 12, 18, and 24 [ Time Frame: Visits 1 (Week -2), 11 (Month 3), 12 (Month 6), 13 (Month 9), 14 (Month 12), 16 (Month 18), and 18 (Month 24) ]Tumor size was measured by computed tomography (CT) scan and was computed as the sum of product of diameters (SPD) for the indicator lesions. CT scans with contrast of the neck, thorax, abdomen, and pelvis were performed at Screening and during the follow-up period (Month 3, 6, 9, 12, 18, and 24). The change in tumor size from Screening (Visit 1) was presented per Radiologist 1 (R1) and Radiologist 2 (R2). Percent change from Screening (Visit 1, Week -2) = (value at Visits 11, 12, 13, 14, 16, and 18 minus the value at Visit 1 divided by the value at Visit 1) * 100.
- Percent Change From Baseline (Visit 2) in CD19+ and CD20+ Cells in Peripheral Blood at Visits 11 and 12 [ Time Frame: Visits 2 (Baseline), 11 (Month 3), and 12 (Month 6) ]CD19 and CD20 are proteins found on the cell surface of B cells, and they can be detected in peripheral blood by flow cytometry. Flow cytometry of peripheral blood was performed for immediate analysis of cells with cluster of differentiation 19 (CD19+) and CD20+. The analysis will be done until a value is reached that is in the normal range. Percent change from Baseline (Visit 2) = (value at Visits 11 and 12 minus the value at Visit 2 divided by the value at Visit 2) * 100.
- Number of Participants With Conversion and no Conversion of BCL2 Positive to BCL2 Negative in Peripheral Blood [ Time Frame: Screening (Visit 1) until Month 24 (Visit 18) ]B-cell lymphoma 2 (BCL2) is the second member of a range of proteins initially described in chromosomal translocations involving chromosomes 14 and 18 in follicular lymphomas. BCL2 mitochondrial ribonucleic acid (mRNA) was measured by polymerase chain reaction (PCR) from peripheral blood. Participants who had no post-screening data were categorized as "Missing."
- Number of Participants Who Experienced Any Adverse Event From First Treatment (Visit 2) to Visit 18 (Month 24) [ Time Frame: From first treatment (Visit 2) until Visit 18 (Month 24) ]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 this treatment. A list of AEs experienced in the study at a frequency threshold of 5% can be found in the AE section.
- Number of Participants With Positive Human Anti-human Antibodies (HAHA) at Visits 1, 12, 13, and 14 [ Time Frame: Visits 1 (Screening), 12 (Month 6), 13 (Month 9), and 18 (Month 24) ]HAHA are indicators of immunogenicity to ofatumumab. Blood samples were withdrawn from participants at Visits 1, 12, 13, and 18 for analysis of HAHA. Analysis of HAHA was done in batches.
- Complement (CH50) Levels at Visit 1 and at the End of Infusion at Visit 2 [ Time Frame: Visits 1 (Week -2) and 2 (Week 0) ]Blood samples were drawn from participants at Visits 1 and 2 for analysis of complement (CH50) levels. Analysis of CH50 was done in batches, and CH50 levels were measured two hours after the end of study medication infusion. Percent change from Screening (Visit 1, Week -2) = (value at Visit 2 minus the value at Visit 1 divided by the value at Visit 1) * 100.
- Number of Participants Classified as Responders for Fragment C Receptor (FcR) Polymorphism (Poly.) [ Time Frame: From first treatment (Visit 2) until Visit 12 (Month 6) ]FcR poly. affect the affinity with which FcRs interact with immunoglobulin molecules and are prognostic factors that are indicative of altered responsiveness to treatment and/or survival. A blood sample was drawn at Visit 1 for analysis (done in batches of several samples) of FcR poly. (Fcgamma RIIIa Valine/Phenylalanine genotypes [TT=thymidine/thymidine, TG=thymidine/guanine, GG=guanine/guanine] and Fcgamma RIIa Arginine/Histidine genotypes [AA=adenine/adenine, AG=adenine/guanine, GG=guanine/guanine]). Responders must have met the criteria for CR, CRu, or PR at either Month 3 or Month 6. Fc receptor polymorphisms and C1qA-276 results are not included in this results summary.
- Ctrough and Cmax at the Eighth Infusion (Visit 9, Week 7) [ Time Frame: Visit 9 (Week 7; up to 10 months after dose) ]Cmax is defined as the maximum concentration of drug in plasma samples. Ctrough is defined as the trough plasma concentration (measured concentration at the end of a dosing interval [taken directly before the start of the next infusion]).
- AUC(0-inf) and AUC(0-168) After the Eighth Infusion (Visit 9, Week 7) [ Time Frame: Visit 9 (Week 7; up to 10 months after dose) ]AUC is defined as the area under the ofatumumab concentration-time curve as a measure of drug exposure. AUC(0-168) is AUC from the start of infusion to 168 hours after the start of the infusion; AUC(0-inf) is AUC from the start of infusion extrapolated to infinity.
- t1/2 After the Eighth Infusion (Visit 9, Week 7) [ Time Frame: Visit 9 (Week 7; up to 10 months after dose) ]t1/2 is defined as terminal half-life, which is the time required for the amount of the drug in the body to decrease by half.
- CL After the Eighth Infusion (Visit 9, Week 7) [ Time Frame: Visit 9 (Week 7; up to 10 months after dose) ]CL is the clearance of drug from plasma, which is defined as the volume of plasma from which drug is removed per unit time.
- Vss After the Eighth Infusion (Visit 9, Week 7) [ Time Frame: Visit 9 (Week 7; to up 10 months after dose) ]Vss is the volume of distribution at steady state of ofatumumab.
|Study Start Date:||May 2007|
|Study Completion Date:||September 2013|
|Primary Completion Date:||April 2009 (Final data collection date for primary outcome measure)|
Intervention Details:Detailed Description:
Eight weekly infusions of ofatumumab. The first infusion of 300mg ofatumunabDrug: Ofatumumab
followed by 7 weekly infusions of 1000mg ofatumumab
Patients in the study will be randomized into two dose groups. Patients in each dose group will receive one infusion of 300 mg of HuMax-CD20 followed by 7 weekly infusions of either 500 or 1000 mg of HuMax-CD20. Disease status will be assessed every 3 months until month 24.
Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00394836
Please refer to this study by its ClinicalTrials.gov identifier: NCT00394836
|GSK Investigational Site|
|Southampton, United Kingdom, SO16 6YD|
Sponsors and Collaborators
|Study Director:||GSK Clinical Trials||GlaxoSmithKline|