Study of Nivolumab in Patients With Classical Hodgkin's Lymphoma (Registrational) (CheckMate 205)
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| ClinicalTrials.gov Identifier: NCT02181738 |
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Recruitment Status :
Completed
First Posted : July 4, 2014
Results First Posted : December 11, 2018
Last Update Posted : January 25, 2023
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Sponsor:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Bristol-Myers Squibb
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Brief Summary:
The purpose of this study is to evaluate the efficacy and safety of Nivolumab in previously treated (cohorts, A, B & C) or newly diagnosed (cohort D) classical Hodgkin Lymphoma participants.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Hodgkin Disease | Drug: Nivolumab Drug: Doxorubicin Drug: Vinblastine Drug: Dacarbazine | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 294 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Non-Comparative, Multi-Cohort, Single Arm, Open-Label, Phase 2 Study of Nivolumab (BMS-936558) in Classical Hodgkin Lymphoma (cHL) Subjects |
| Actual Study Start Date : | August 12, 2014 |
| Actual Primary Completion Date : | August 31, 2017 |
| Actual Study Completion Date : | December 27, 2022 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Nivolumab
| Arm | Intervention/treatment |
|---|---|
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Experimental: Nivolumab (Cohort A, B, C and D)
Cohort (A, B, C): Nivolumab: Specified dose on specified days Cohort (D): Nivolumab: Specified dose on specified days + Doxorubicin: Specified dose on specified days + Vinblastine: Specified dose on specified days + Dacarbazine: Specified dose on specified days |
Drug: Nivolumab
Specified dose on specified days
Other Name: BMS-936558 Drug: Doxorubicin Specified dose on specified days Drug: Vinblastine Specified dose on specified days Drug: Dacarbazine Specified dose on specified days |
Primary Outcome Measures :
- Objective Response Rate (ORR) Based on IRRC Assessments in Cohorts A, B, and C [ Time Frame: From the date of first study drug dose up to approximately 28 months ]To assess the clinical benefit of nivolumab, as measured by ORR based on IRRC assessment, and defined as proportion of subjects achieving either a PR or CR according to the 2007 IWG criteria. Analyses of efficacy endpoints were performed separately for each cohort, according to IWG 2007. For cohort A and B, if the bone marrow was involved by lymphoma before treatment, the infiltrate must have cleared on repeat bone marrow biopsy. For cohort C, no evidence of FDG-avid disease in bone marrow will be required in all patients in lieu of bone marrow aspirate/ biopsy.
- Duration of Objective Response in Cohorts A, B, and C [ Time Frame: From the date of first study drug dose up to approximately 28 months ]DOR was defined as the time from first response (CR or PR) to the date of the first documented tumor progression as determined by the investigator using the 2007 IWG criteria or death due to any cause, whichever occurred first. Appearance of any new lesion > 1.5 cm in any axis during or at the end of therapy, even if other lesions are decreasing in size. Increased FDG uptake in a previously unaffected site should only be considered relapsed or PD after confirmation with other modalities.
- Complete Remission Rate in Cohorts A, B, and C [ Time Frame: From the date of first study drug dose up to approximately 28 months ]The CR rate was defined as the number of subjects with a BOR of CR according to the 2007 IWG criteria, based on IRRC assessment, divided by the number of treated subjects.
- Duration of Complete Remission (CR) for Cohorts A, B, and C [ Time Frame: from date of first documented CR up to approximately 28 months ]The CR rate was defined as the number of subjects with a BOR of CR according to the 2007 IWG criteria, based on IRRC assessment, divided by the number of treated subjects. The duration of CR was only evaluated in subjects with BOR of CR and was defined as the time from first documentation of CR (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 occurred later) to the date of initial objectively documented progression as determined using the 2007 IWG criteria or death due to any cause, whichever occurred first. Censoring was applied as per DOR definition.
- Number of Participants Who Experienced at Least One Treatment Related Grade 3-5 AE in Cohort D [ Time Frame: From last dose up to 120 days ]To evaluate the safety and tolerability of nivolumab monotherapy during the monotherapy phase and the safety and tolerability of nivolumab in combination with AVD during the combination phase
Secondary Outcome Measures :
- Partial Remission (PR) Rate in Cohorts A, B, and C [ Time Frame: From the time of the first documented PR up to approximately 28 months ]The PR rate was defined as the number of subjects with a BOR of PR according to the 2007 IWG criteria, based on IRRC assessment, divided by the number of treated subjects.
- Duration of PR in Cohorts A, B, and C [ Time Frame: From the time of the first documented PR up to approximately 28 months ]The duration of PR was only evaluated in subjects with BOR of PR and was defined as the time from first documentation of PR to the date of initial objectively documented progression as determined using the 2007 IWG criteria or death due to any cause, whichever occurred first. Censoring was applied as per DOR definition.
- ORR Based on Investigator Assessments for Cohorts A, B, and C [ Time Frame: From the first dose to first progression, death, or start of other therapy up to 28 months ]Investigator-assessed ORR and DOR were defined similarly as described for ORR and DOR per IRRC assessment above, but were assessed per investigator using the 2007 IWG criteria.
- Duration of Objective Response (DOR) Based on Investigator Assessments in Cohorts A, B, and C [ Time Frame: From the date of first study drug dose up to approximately 28 months ]Investigator-assessed ORR and DOR were defined similarly as described for ORR and DOR per IRRC assessment above, but were assessed per investigator using the 2007 IWG criteria.
- Treatment Discontinuation Rate in Cohort D [ Time Frame: From date of first dose to end of combination therapy up to 28 months ]Subjects were treated with four doses of nivolumab flat dose 240 mg IV every 2 weeks (monotherapy phase), followed by twelve doses of the combination of AVD (Adriamycin/ doxorubicin 25 mg/m2, vinblastine 6 mg/m2, dacarbazine 375 mg/m2) chemotherapy and nivolumab flat dose 240 mg IV for 6 cycles (combination phase). Each 28-day dosing period constituted a Combocycle: two doses of the combination therapy per cycle, except for Combocycle 6, which was only a 15-day cycle. The combination therapy was administered every 2 weeks for 12 doses (two doses, Dose 1 on Day 1 and Dose 2 on Day 15, of each Combocycle x 6 cycles). The combination phase ended at Dose 2 (Day 15) of Combocycle 6. The primary analysis for Cohort D was conducted when all treated patients for Cohort D had completed follow-up visit 1 and end-of- therapy response assessment. All analyses for Cohort D were performed separately from other cohorts.
- Incidence of Deaths in Cohort D [ Time Frame: From first dose up to 28 months ]Safety was analyzed through the incidence of deaths, adverse events, serious adverse events, adverse events leading to discontinuation, adverse events leading to dose delay, select adverse events and specific laboratory abnormalities (worst grade). Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Safety of subjects was analyzed per treatment phase (monotherapy phase, combination therapy phase) and overall.
- Incidence of Adverse Events (AEs) in Cohort D [ Time Frame: From last dose up to 120 days ]Safety was analyzed through the incidence of deaths, adverse events, serious adverse events, adverse events leading to discontinuation, adverse events leading to dose delay, select adverse events and specific laboratory abnormalities (worst grade). Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Safety of subjects was analyzed per treatment phase (monotherapy phase, combination therapy phase) and overall.
- Incidence of Serious Adverse Events (SAEs) in Cohort D [ Time Frame: From last dose up to 120 days ]Safety was analyzed through the incidence of deaths, adverse events, serious adverse events, adverse events leading to discontinuation, adverse events leading to dose delay, select adverse events and specific laboratory abnormalities (worst grade). Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Safety of subjects was analyzed per treatment phase (monotherapy phase, combination therapy phase) and overall.
- Incidence of AEs Leading to Discontinuation in Cohort D [ Time Frame: From last dose up to 120 days ]Safety was analyzed through the incidence of deaths, adverse events, serious adverse events, adverse events leading to discontinuation, adverse events leading to dose delay, select adverse events and specific laboratory abnormalities (worst grade). Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Safety of subjects was analyzed per treatment phase (monotherapy phase, combination therapy phase) and overall.
- Incidence of AEs Leading to Dose Delay in Cohort D [ Time Frame: From last dose up to 120 days ]Safety was analyzed through the incidence of deaths, adverse events, serious adverse events, adverse events leading to discontinuation, adverse events leading to dose delay, select adverse events and specific laboratory abnormalities (worst grade). Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Safety of subjects was analyzed per treatment phase (monotherapy phase, combination therapy phase) and overall.
- Incidence of Select AEs in Cohort D [ Time Frame: From last dose up to 120 days ]Select AEs have been categorized into seven areas: pulmonary toxicity, gastrointestinal toxicity, hepatotoxicity, endocrinopathy, skin toxicity, neurological toxicity and renal toxicity. Select AEs, in particular pneumonitis, are considered clinically meaningful as they require greater vigilance and for early recognition and prompt intervention.
- Incidence of Grade 3-4 Laboratory Abnormalities in Cohort D [ Time Frame: From last dose up to 120 days ]Specific laboratory abnormalities (worst grade).
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Must have received prior high-dose conditioning chemotherapy followed by autologous stem cell transplant (ASCT) as a part of salvage therapy for cHL (cohort A, B & C - enrollment closed)
- Participants may be Brentuximab vedotin- naïve, or may have had prior Brentuximab vedotin treatment (cohort A, B & C - enrollment closed)
- Newly diagnosed and previously untreated classical Hodgkin Lymphoma (cohort D)
Exclusion Criteria:
- Known central nervous system lymphoma
- Participants with nodular lymphocyte-predominant Hodgkin Lymphoma
- Prior allogeneic stem cell transplantation (SCT)
- Chest radiation ≤ 24 weeks prior to first dose
- Carmustine ≥ 600 mg/m² received as part of the pre-transplant conditioning regimen
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02181738
Locations
Show 38 study locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
| Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
Study Documents (Full-Text)
Documents provided by Bristol-Myers Squibb:
Documents provided by Bristol-Myers Squibb:
Study Protocol [PDF] September 8, 2016
Statistical Analysis Plan [PDF] June 8, 2018
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Bristol-Myers Squibb |
| ClinicalTrials.gov Identifier: | NCT02181738 |
| Other Study ID Numbers: |
CA209-205 2014-001509-42 ( EudraCT Number ) |
| First Posted: | July 4, 2014 Key Record Dates |
| Results First Posted: | December 11, 2018 |
| Last Update Posted: | January 25, 2023 |
| Last Verified: | January 2023 |
Additional relevant MeSH terms:
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Hodgkin Disease Lymphoma Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Doxorubicin Nivolumab Dacarbazine Vinblastine Antibiotics, Antineoplastic |
Antineoplastic Agents Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Immunological Immune Checkpoint Inhibitors Antineoplastic Agents, Alkylating Alkylating Agents Antineoplastic Agents, Phytogenic Tubulin Modulators Antimitotic Agents Mitosis Modulators |