Study of Nivolumab in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) That Have Either Failed or Are Not Eligible for Autologous Stem Cell Transplant (CheckMate 139)

Study Overview
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Brief Summary
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The purpose of this study is to determine whether Nivolumab is effective in the treatment of DLBCL in patients that have failed or are ineligible for ASCT

Official Title
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A Single-Arm, Open-Label, Phase 2 Study of Nivolumab (BMS-936558) in Subjects With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) After Failure of Autologous Stem Cell Transplant (ASCT) or After Failure of At Least Two Prior Multi-Agent Chemotherapy Regimens in Subjects Who Are Not Candidates for ASCT

Conditions
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Lymphoma. Non-Hodgkin

Intervention / Treatment
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* Drug: Nivolumab


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Confirmation of relapsed or refractory DLBCL or transformed lymphoma (TL) Eastern Cooperative Oncology Group (ECOG) performance status of 0 -1 At least one lesion that measures >1.5 cm Prior therapy and screening lab criteria must be met Appropriate contraceptive measures must be taken Exclusion Criteria: Known central nervous system (CNS) lymphoma History of interstitial lung disease, prior malignancy, active autoimmune disease, positive test for hepatitis B or hepatitis C virus Prior allogeneic stem cell transplant (SCT), chest radiation ≤ 24 weeks from study drug, ≥1000 mg of Carmustine Bis-chloroethylnitrosourea (BCNU) as part of pre-transplant conditioning regimen, prior treatment with drug targeting T-cell costimulation or immune checkpoint pathways Women who are breastfeeding or pregnant

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: Nivolumab (3 mg/kg)<br>Nivolumab 3 mg/kg solution intravenously every 2 weeks until progression or unacceptable toxicity | Drug: Nivolumab<br> <br> * Other names: BMS-936558;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) Per Independent Radiologic Review Committee (IRRC) Assessment | ORR is defined as the percentage of participants with a Best Overall Response (BOR) of Complete Remission (CR) or Partial Remission (PR), according to the 2007 revised International Working Group (IWG) Criteria for Malignant Lymphoma, , based on IRRC assessment. CR= Disappearance of all evidence of disease, confirmed by PET scan; PR= Regression of measurable disease and no emergence of new sites | From first dose until date of documented disease progression or subsequent therapy, whichever occurs first (assesed up to April 2016, approximately 25 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DOR) | DOR is defined as the time from first response (Complete Response (CR) or Partial Response (PR)) to the date of initial objectively documented progression as determined using the 2007 revised IWG Criteria for Malignant Lymphoma, based on Independent Radiology Review Committee (IRRC) assessment, or death due to any cause, whichever occurs first. CR= Disappearance of all evidence of disease, confirmed by PET scan; PR= Regression of measurable disease and no emergence of new sites. | From date of first response to the date of documented disease progression or death, whichever occurs first (up to approximately 18 months) | 
| Complete Remission Rate | Complete Remission Rate is defined as the percentage of participants with a Best Overall Response (BOR) of Complete Response (CR) according to the 2007 revised IWG Criteria for Malignant Lymphoma, based on Independent Radiology Review Committee (IRRC) assessment. CR= Disappearance of all evidence of disease, confirmed by PET scan. | From date of first dose to study completion (up to approximately 78 months) | 
| Duration of Complete Remission | The duration of Complete Remission is defined as the time from first documentation of Complete Response (CR) (which is the date of first negative FDG-PET scan or the date of first documentation of no disease involvement in the bone marrow [if required], whichever occurs later) to the date of initial objectively documented progression as determined using the 2007 IWG criteria, based on Independent Radiology Review Committee (IRRC) assessment, or death due to any cause, whichever occurs first. CR= Disappearance of all evidence of disease, confirmed by PET scan. | From time of first documentation of CR to the date of initial documented disease progression or death due to any cause, whichever occurs first (up approximately 14 months) | 
| Partial Remission Rate | Partial Remission rate is defined as the percentage of participants with a Best Overall Response (BOR) of Partial Response (PR) according to the 2007 revised IWG Criteria for Malignant Lymphoma, based on Independent Radiology Review Committee (IRRC) assessment. PR= Regression of measurable disease and no emergence of new sites. | From date of first dose to study completion (up to approximately 78 months) | 
| Duration of Partial Remission | Duration of Partial Remission is defined as the time from first documentation of Partial Response (PR) to the date of initial objectively documented progression as determined using the 2007 IWG criteria, based on Independent Radiology Review Committee (IRRC) assessment, or death due to any cause, whichever occurs first. PR= Regression of measurable disease and no emergence of new sites. | From date of first documentation of PR to date of disease progression or death due to any cause, whichever occurs first (up to approximately 12 months) | 
| Progression Free Survival | Progression Free Survival (PFS) is defined as the time from first dosing date to the date of the first documented progression, as determined by an Independent Radiology Review Committee (IRRC) according to the 2007 revised IWG Criteria for Malignant Lymphoma, or death due to any cause, whichever occurs first. | From date of first dose to date of documented disease progression or death due to any cause, whichever occurs first (up to approximately 2 months) | 
| Objective Response Rate (ORR) Per Investigator Assessment | ORR is defined as the percentage of participants with a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR), according to investigator assessment. CR= Disappearance of all evidence of disease, confirmed by PET scan; PR= Regression of measurable disease and no emergence of new sites. | From first dose until date of documented disease progression or subsequent therapy, whichever occurs first (up to approximately 30 months) |