Efficacy and Safety Study of MDV9300 in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of MDV9300 in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) that have achieved either stable disease or a partial remission following definitive salvage therapy. Two cohorts of patients will be enrolled: a cohort treated with salvage chemotherapy but considered ineligible for autologous stem cell transplant (ASCT), and a cohort of patients who have received ASCT following salvage chemotherapy.

Official Title
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An International, Phase 2, Open-Label, Efficacy and Safety Study of MDV9300 in Patients With an Incomplete Response Following Salvage Therapy or Autologous Stem Cell Transplantation for Relapsed or Refractory CD20+ Diffuse Large B-Cell Lymphoma

Conditions
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Lymphoma, Large B-Cell, Diffuse, Primary Mediastinal Large B-cell Lymphoma, Transformed Indolent Lymphoma

Intervention / Treatment
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* Biological: MDV9300


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older and willing and able to provide informed consent; Histologically confirmed relapsed or refractory CD20+ DLBCL, transformed indolent lymphoma (follicular or other), or primary mediastinal large B-cell lymphoma; Received prior treatment with a standard anthracycline and therapeutic anti-CD20 monoclonal antibody-based regimen; For transplant-ineligible patients, salvage therapy just prior to MDV9300 treatment must have resulted in a PR or stable disease; For post autologous stem cell transplant (ASCT) patients, salvage therapy plus ASCT just prior to MDV9300 treatment must have resulted in a PR or stable disease; Adequate bone marrow reserve as defined per protocol; Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1. Patients with stable ECOG scores of 2 may be allowed with medical monitor approval. Exclusion Criteria: Burkitt, mantle cell, follicular, or mucosa-associated lymphoid tissue lymphoma History of serious autoimmune disease; History of central nervous system involvement of lymphoma; Prior therapy with agents targeting immune coinhibitory receptors.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MDV9300<br> | Biological: MDV9300<br>* MDV9300 will be administered at a dose of 200 mg by intravenous (IV) infusion every 2 weeks until treatment discontinuation criteria are met.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best overall response rate | Defined as the proportion of patients in the intent-to-treat population with a complete response (CR) or partial response (PR) attributable to study treatment, as assessed by the independent review committee (IRC). | no later than 6 months after the last patient is enrolled in a cohort | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of response (for responders) | Defined as the time from the first objective evidence of CR or PR as assessed by the IRC to the first objective evidence of disease progression or death due to any cause, whichever occurs first. | no later than 6 months after the last patient is enrolled in a cohort | 
| Progression-free survival | Defined as the time from the date of first study drug infusion to the first objective evidence of disease progression or death due to any cause, whichever occurs first. | no later than 6 months after the last patient is enrolled in a cohort | 
| Time to response (for responders) | Defined as the time from the date of first study drug infusion to the first objective evidence of CR or PR as assessed by the IRC. | no later than 6 months after the last patient is enrolled in a cohort | 
| Overall survival | Defined as the time from the date of first study drug infusion to death due to any cause. | no later than 6 months after the last patient is enrolled in a cohort | 
| Composite of safety | Safety will be evaluated by incidence and severity of adverse events, including serious adverse events and incidence of permanent treatment discontinuation due to adverse events. | no later than 6 months after the last patient is enrolled in a cohort |