Ofatumumab in Patients With Relapsed/Progressive Diffused Large B-Cell Lymphoma (DLBCL) Ineligible for or Relapse/Progression After Transplant
|ClinicalTrials.gov Identifier: NCT00622388|
Recruitment Status : Completed
First Posted : February 25, 2008
Results First Posted : September 8, 2011
Last Update Posted : July 24, 2015
|Condition or disease||Intervention/treatment||Phase|
|Lymphoma, Large-Cell, Diffuse||Drug: Ofatumumab||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||81 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open-label, Single-arm. Multi-center Phase 2 Trial With Ofatumumab in Patients With Relapsed/Progressive Diffuse Large B-Cell Lymphoma (DLBCL) Ineligible for Transplant or Relapse/Progression After Autologous Transplant|
|Study Start Date :||December 2007|
|Primary Completion Date :||May 2010|
|Study Completion Date :||August 2014|
8 weekly intra-venous (I.V.) infusions, 1 x 300mg and 7 x 1000mg
8 weekly intra-venous (i.v.) infusions, 1 x 300mg and 7 x 1000mg
- Number of Participants With Objective Response [ Time Frame: 6-month period from start of treatment (up to Week 24) ]Objective response of ofatumumab treatment was assessed according to the "revised response criteria for malignant lymphoma." Participants with objective response were defined as responders with complete remission (CR) or partial remission (PR) of disease. CR is defined as the disappearance of all evidence of disease, and PR is defined as the regression of measurable disease with no new sites of disease.
- Number of Participants Classified as Responders and Non-responders for Objective Response [ Time Frame: 6-month period from start of treatment (up to Week 24) ]According to the "revised response criteria for malignant lymphoma," responders included participants with CR and PR, and non-responders included participants with stable disease (SD) and progressive disease (PD). Participants not evaluable (NE) were also considered to be non-responders. PD is defined as any new lesion or an increase by more than or equal to 50% of previously involved sites from baseline. SD is defined as failure to attain CR, PR, or PD.
- Duration of Response [ Time Frame: From date of start of treatment to 2 years or withdrawal ]The duration of response was defined as the time from the initial response (CR or PR) to the time of relapse, progression, or death. If the participant was lost to follow-up, the endpoint was censored, and the censoring date was the date of the last attended visit at which the endpoint was assessed.
- Progression-free Survival (PFS) [ Time Frame: From date of start of treatment to 2 years or withdrawal ]PFS was defined as the time from treatment start until progression or death.
- Time to Next Diffuse Large B-Cell Lymphoma (DLBCL) Therapy [ Time Frame: From date of start of treatment to 5 years or withdrawal ]Time to next DLBCL therapy was defined as the time from the first infusion date to the time of the first administration of the next DLBCL treatment other than ofatumumab. If the participants were lost to follow-up, the endpoint was censored, and the censoring date was the date of the last attended visit at which the endpoint was assessed.
- Overall Survival (OS) [ Time Frame: From date of start of treatment to 5 years or withdrawal ]Overall survival is defined as the time from first infusion to death. Overall survival was a secondary endpoint in the study. However, since many participants withdrew from the study after developing disease progression overall survival could not be reliably estimated.
- Number of Participants With Positive Human Anti-human Antibodies (HAHA) at Screening and at Visits 12, 13, 14, and 18 [ Time Frame: Screening visit (=<14 days before treatment start), Visit 12 (Month 6), Visit 13 (Month 9), Visit 14 (Month 12), and Visit 18 (Month 24) ]HAHA are indicators of immune response to ofatumumab. Blood samples were collected from participants at Visits 1, 12, 13, 14, and 18 and analyzed in batches. The number of participants with positive results at each visit is reported.
- Median Percent Change From Baseline in CD45+CD19+ and CD45+CD20+ Cells in the Peripheral Blood at the Indicated Visits [ Time Frame: Baseline and Visit 10 (Week 8), Visit 11 (Week 11), Visit 12 (Month 6), Visit 13 (Month 9), Visit 14 (Month 12), Visit 15 (Month 15), Visit 16 (Month 18), Visit 17 (Month 21), Visit 18 (Month 24), Visit 19 (Month 30), Visit 20 (Month 36) ]B cells (CD45+CD19+ and CD45+CD20+) were measured in peripheral blood samples by flow cytometry. Percent change from Baseline = (value at the indicated visits minus the value at Baseline divided by the value at Baseline) * 100.
- Number of Participants Who Experienced at Least One Adverse Event (AE) [ Time Frame: Time frame is from date of start of treatment to 2 years or withdrawal ]An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. The protocol-defined AE reporting period was from the first infusion (Visit 2/Week 0) to Visit 18 (Month 24 of follow-up) or time of withdrawal (treatment and follow-up).
- Percent Change From Screening in Complement (CH50) Levels [ Time Frame: Screening and post-baseline visits (last visit was to occur 24 months post first dose) ]CH50 was mistakenly registered as an outcome measure with the protocol record. Samples were not collected, and no analysis will take place. Thus, no data will be reported for this outcome measure.
- AUC(0-inf) and AUC(0-168) for Ofatumumab at the Eighth Infusion [ Time Frame: Visit 9 (Week 7; up to 11 months after last dose) ]AUC is defined as the area under the ofatumumab concentration-time curve as a measure of drug exposure. AUC(0-168) is the AUC from the start of infusion to 168 hours after the start of the infusion; AUC(0-inf) is the AUC from the start of infusion extrapolated to infinity.
- Cmax and Ctrough for Ofatumumab at the First and Eighth Infusions [ Time Frame: Visit 2 (Week 0) and Visit 9 (Week 7) ]Cmax is defined as the maximum concentration of drug in serum samples. Ctrough is defined as the minimum observed concentration prior to the start of the next dose. No drug is present prior to the first infusion; therefore, there are no Ctrough results for the first dose.
- Half-life (T1/2) for Ofatumumab at the Eighth Infusion [ Time Frame: Visit 9 (Week 7; up to 11 months after last dose) ]t1/2 is defined as terminal half-life and is the time required for the amount of drug in the body to decrease by half.
- Clearance (CL) of Ofatumumab at the Eighth Infusion [ Time Frame: Visit 9 (Week 7; up to 11 months after last dose) ]CL is the clearance of drug from serum, which is defined as the volume of serum from which the drug is cleared per unit time.
- Volume of Distribution at Steady State (Vss) of Ofatumumab at the Eighth Infusion [ Time Frame: Visit 9 (Week 7; up to 11 months after the last dose) ]Vss is the volume of distribution at steady state of ofatumumab.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00622388
|GSK Investigational Site|
|London, United Kingdom, EC1M 6BQ|
|Study Director:||GSK Clinical Trials||GlaxoSmithKline|