Ofatumumab in Patients With Relapsed/Progressive Diffused Large B-Cell Lymphoma (DLBCL) Ineligible for or Relapse/Progression After Transplant

Study Overview
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Brief Summary
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The purpose of this trial is to determine the effect of ofatumumab in patients with Diffused Large B-Cell Lymphoma (DLBCL) ineligible for transplant or relapsed after autologous transplant

Official Title
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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

Conditions
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Lymphoma, Large-Cell, Diffuse

Intervention / Treatment
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* Drug: Ofatumumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with DLBCL and relapse after complete remission or disease progression after partial remission who are ineligible for autologous stem cell transplantation and relapse after complete remission or disease progression after partial remission following autologous stem cell transplantation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ofatumumab<br>8 weekly intra-venous (I.V.) infusions, 1 x 300mg and 7 x 1000mg | Drug: Ofatumumab<br>* 8 weekly intra-venous (i.v.) infusions, 1 x 300mg and 7 x 1000mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Objective Response | 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. | 6-month period from start of treatment (up to Week 24) | 
| Number of Participants Classified as Responders and Non-responders for Objective Response | 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. | 6-month period from start of treatment (up to Week 24) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response | 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. | From date of start of treatment to 2 years or withdrawal | 
| Progression-free Survival (PFS) | PFS was defined as the time from treatment start until progression or death. | From date of start of treatment to 2 years or withdrawal | 
| Time to Next Diffuse Large B-Cell Lymphoma (DLBCL) Therapy | 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. | From date of start of treatment to 5 years or withdrawal | 
| Overall Survival (OS) | 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. | From date of start of treatment to 5 years or withdrawal | 
| Number of Participants With Positive Human Anti-human Antibodies (HAHA) at Screening and at Visits 12, 13, 14, and 18 | 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. | Screening visit (=<14 days before treatment start), Visit 12 (Month 6), Visit 13 (Month 9), Visit 14 (Month 12), and Visit 18 (Month 24) | 
| Median Percent Change From Baseline in CD45+CD19+ and CD45+CD20+ Cells in the Peripheral Blood at the Indicated Visits | 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. | 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) | 
| Number of Participants Who Experienced at Least One Adverse Event (AE) | 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). | Time frame is from date of start of treatment to 2 years or withdrawal | 
| Percent Change From Screening in Complement (CH50) Levels | 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. | Screening and post-baseline visits (last visit was to occur 24 months post first dose) | 
| AUC(0-inf) and AUC(0-168) for Ofatumumab at the Eighth Infusion | 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. | Visit 9 (Week 7; up to 11 months after last dose) | 
| Cmax and Ctrough for Ofatumumab at the First and Eighth Infusions | 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. | Visit 2 (Week 0) and Visit 9 (Week 7) | 
| Half-life (T1/2) for Ofatumumab at the Eighth Infusion | 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. | Visit 9 (Week 7; up to 11 months after last dose) | 
| Clearance (CL) of Ofatumumab at the Eighth Infusion | 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. | Visit 9 (Week 7; up to 11 months after last dose) | 
| Volume of Distribution at Steady State (Vss) of Ofatumumab at the Eighth Infusion | Vss is the volume of distribution at steady state of ofatumumab. | Visit 9 (Week 7; up to 11 months after the last dose) |