Study of Nivolumab in Patients With Classical Hodgkin's Lymphoma (Registrational) (CheckMate 205)

• ClinicalTrials.gov Identifier: NCT02181738
• Recruitment Status: Completed
• First Posted: July 4, 2014
• Results First Posted: December 11, 2018
• Last Update Posted: November 28, 2023
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: July 1, 2014
• First Posted Date: July 4, 2014
• Results First Submitted Date: August 31, 2018
• Results First Posted Date: December 11, 2018
• Last Update Posted Date: November 28, 2023
• Actual Study Start Date: August 12, 2014
• Actual Primary Completion Date: August 31, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 27, 2023)

• Objective Response Rate (ORR) Based on IRRC Assessments in Cohorts A, B, and C [ Time Frame: From first dose to the date of initial objectively documented progression or the date of subsequent therapy, whichever occurred first (up to approximately 28 months) ]
  ORR is the percent of participants achieving either a complete remission (CR) or partial remission (PR) 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 was required in all participants in lieu of bone marrow aspirate/ biopsy. CR is the percent of participants with a best overall response (BOR) of CR (disappearance of all evidence of disease) according to the 2007 IWG criteria, based on IRRC assessment. PR is the percent of participants with a best overall response (BOR) of PR (regression of measurable disease and no new sites) according to the 2007 IWG criteria, based on IRRC assessment. Confidence interval based on Clopper-Pearson method.
• Number of Participants Who Experienced at Least One Treatment Related Grade 3-5 AE in Cohort D [ Time Frame: From first dose of the considered therapy phase to 30 days after last dose of study therapy phase (or up to first dose of combination if any when considering the monotherapy period) (an average of 8 months and a maximum of 11 months) ]
  An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation subject administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug.

• Original Primary Outcome Measures (submitted: July 3, 2014): Number of subjects with a best overall response (BOR) of CR or PR, according to the 2007 International Working Group (IWG) criteria, based on Independent Radiographic Review Committee assessment, divided by the number of treated subjects [ Time Frame: Up to one year after last patient first treatment ]

Current Secondary Outcome Measures (submitted: November 27, 2023)

• Duration of Objective Response Based on IRRC Assessments in Cohorts A, B, and C [ Time Frame: From first dose to the date of initial objectively documented progression or the date of subsequent therapy, or death whichever occurred first (up to approximately 100 months). ]
  DOR is the time from first response (complete remission (CR) or partial remission (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. For participants who neither progressed nor died, the DOR was censored on the date of their last tumor assessment. Participants who started subsequent therapy without a prior reported progression were censored at the last tumor assessments prior to initiation of the subsequent anticancer therapy. CR is the percent of participants with a best overall response (BOR) of CR (disappearance of all evidence of disease) according to the 2007 IWG criteria, based on IRRC assessment. PR is the percent of participants with a best overall response (BOR) of PR (regression of measurable disease and no new sites) according to the 2007 IWG criteria, based on IRRC assessment. Computed using Kaplan-Meier method.
• Complete Remission (CR) Rate Based on IRRC Assessments in Cohorts A, B, and C [ Time Frame: From first dose to the date of initial objectively documented progression or the date of subsequent therapy, or death whichever occurred first (up to approximately 100 months) ]
  The CR rate was defined as the percent of participants with a BOR of CR (disappearance of all evidence of disease) according to the 2007 IWG criteria, based on IRRC assessment. Confidence interval based on Clopper-Pearson method.
• Duration of Complete Remission (CR) Based on IRRC Assessments for Cohorts A, B, and C [ Time Frame: From first dose to the date of initial objectively documented progression or the date of subsequent therapy, or death whichever occurred first (up to approximately 100 months) ]
  The duration of CR was only evaluated in participants 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 (Any new lesion or increase by >=50% of previously involved sites from nadir) as determined using the 2007 IWG criteria or death due to any cause, whichever occurred first. Censoring was applied as per DOR definition. Computed using Kaplan-Meier method.
• Partial Remission (PR) Rate Based on IRRC Assessments in Cohorts A, B, and C [ Time Frame: From first dose to the date of initial objectively documented progression or the date of subsequent therapy, or death whichever occurred first (up to approximately 100 months) ]
  The PR rate was defined as the percent of participants with a BOR of PR (regression of measurable disease and no new sites) according to the 2007 IWG criteria, based on IRRC assessment. Confidence interval based on Clopper-Pearson method.
• Duration of PR Based on IRRC Assessments in Cohorts A, B, and C [ Time Frame: From first dose to the date of initial objectively documented progression or the date of subsequent therapy, or death whichever occurred first (up to approximately 100 months) ]
  The duration of PR was only evaluated in participants with BOR of PR and was defined as the time from first documentation of PR (regression of measurable disease and no new sites) to the date of initial objectively documented progression (any new lesion or increase by >=50% of previously involved sites from nadir) as determined using the 2007 IWG criteria or death due to any cause, whichever occurred first. Censoring was applied as per DOR definition. Computed using Kaplan-Meier method.
• Objective Response Rates (ORR) Based on Investigator Assessments for Cohorts A, B, and C [ Time Frame: From first dose to the date of initial objectively documented progression or the date of subsequent therapy, or death whichever occurred first (up to approximately 100 months) ]
  ORR is the percent of participants achieving either a complete remission (CR) or partial remission (PR) 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 was required in all participants in lieu of bone marrow aspirate/ biopsy. CR is the percent of participants with a best overall response (BOR) of CR (disappearance of all evidence of disease) according to the 2007 IWG criteria, based on IRRC assessment. PR is the percent of participants with a best overall response (BOR) of PR (regression of measurable disease and no new sites) according to the 2007 IWG criteria, based on IRRC assessment. Confidence interval based on Clopper-Pearson method.
• Duration of Objective Response (DOR) Based on Investigator Assessments in Cohorts A, B, and C [ Time Frame: From first dose to the date of initial objectively documented progression or the date of subsequent therapy, or death whichever occurred first (up to approximately 100 months) ]
  DOR is the time from first response (complete remission (CR) or partial remission (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. For participants who neither progressed nor died, the DOR was censored on the date of their last tumor assessment. Participants who started subsequent therapy without a prior reported progression were censored at the last tumor assessments prior to initiation of the subsequent anticancer therapy. CR is the percent of participants with a best overall response (BOR) of CR (disappearance of all evidence of disease) according to the 2007 IWG criteria, based on IRRC assessment. PR is the percent of participants with a best overall response (BOR) of PR (regression of measurable disease and no new sites) according to the 2007 IWG criteria, based on IRRC assessment. Computed using Kaplan-Meier method.
• Treatment Discontinuation Rate in Cohort D [ Time Frame: From first dose up until the date of treatment discontinuation (up to approximately 100 months). ]
  Treatment discontinuation rate (TDR) is the number of treated participants who received <4 doses of monotherapy or <12 doses of their assigned combination regimen. A participant is considered as having received an AVD/NAVD dose as soon as they received at least one drug of AVD/NAVD for the considered dose. Participants must have received at least one dose of Nivolumab during the combination therapy phase to be included in participants treated with NAVD. If a participant subsequently met Criteria to Resume Nivolumab Dosing, the combination of nivolumab and AVD could be used. Participants who underwent treatment beyond progression during the Monotherapy phase could use the combination of nivolumab and AVD if all 4 doses of nivolumab monotherapy are completed. Discontinuation can be due to any reason including, but not limited to, drug-related toxicity, diseases progression, or death.
• Number of Participants Who Died in Cohort D [ Time Frame: From first dose of the considered therapy phase to 100 days after last dose of study therapy phase (or up to first dose of combination if any when considering the monotherapy period) (an average of 10 months up to a maximum of 13 months) ]
  Number of participants who died in Cohort D within 100 days after last dose of study therapy.
• Number of Participants With Adverse Events (AEs) in Cohort D [ Time Frame: From first dose of the considered therapy phase to 30 days after last dose of study therapy phase (or up to first dose of combination if any when considering the monotherapy period) (an average of 8 months and a maximum of 11 months) ]
  An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Toxicities were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
• Number of Participants With Serious Adverse Events (SAEs) in Cohort D [ Time Frame: From first dose of the considered therapy phase to 30 days after last dose of study therapy phase (or up to first dose of combination if any when considering the monotherapy period) (an average of 8 months and a maximum of 11 months) ]
  A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose results in death, is life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), requires inpatient hospitalization or causes prolongation of existing hospitalization. Toxicities were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
• Number of Participants With AEs Leading to Discontinuation in Cohort D [ Time Frame: From first dose of the considered therapy phase to 30 days after last dose of study therapy phase (or up to first dose of combination if any when considering the monotherapy period) (an average of 8 months and a maximum of 11 months) ]
  An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Toxicities were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
• Number of Participants With AEs Leading to Dose Delay in Cohort D [ Time Frame: From first dose of the considered therapy phase to 30 days after last dose of study therapy phase (or up to first dose of combination if any when considering the monotherapy period) (an average of 8 months and a maximum of 11 months) ]
  An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Toxicities were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
• Number of Participants With Select AEs in Cohort D [ Time Frame: From first dose of the considered therapy phase to 30 days after last dose of study therapy phase (or up to first dose of combination if any when considering the monotherapy period) (an average of 8 months and a maximum of 11 months) ]
  An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Toxicities were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. 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.
• Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests in Cohort D Monotherapy Phase [ Time Frame: From first dose of monotherapy to 30 days after last dose of monotherapy phase (up to approximately 3 months) ]
  The number of participants with laboratory abnormalities in specific thyroid tests based on SI conventional units. TSH = Thyroid Stimulating Hormone LLN = Lower Limit of Normal ULN = Upper Limit of Normal
• Number of Participants Laboratory Abnormalities in Specific Thyroid Tests in Cohort D Combination Therapy Phase [ Time Frame: From first dose of the combination therapy to 30 days after last dose of combination therapy (an average of 8 months and a maximum of 11 months) ]
  The number of participants with laboratory abnormalities in specific thyroid tests based on SI conventional units. TSH = Thyroid Stimulating Hormone LLN = Lower Limit of Normal ULN = Upper Limit of Normal
• Number of Participants With Laboratory Abnormalities in Specific Liver Tests in Cohort D Monotherapy Phase [ Time Frame: From first dose of monotherapy to 30 days after last dose of monotherapy phase (up to approximately 3 months) ]
  The number of participants with laboratory abnormalities in specific liver tests based on SI conventional units. ALT = Alanine Aminotransferase, AST = Aspartate Aminotransferase, ULN = Upper Limit of Normal.
• Number of Participants With Laboratory Abnormalities in Specific Liver Tests in Cohort D Combination Therapy Phase [ Time Frame: From first dose of the combination therapy to 30 days after last dose of combination therapy (an average of 8 months and a maximum of 11 months) ]
  The number of participants with laboratory abnormalities in specific liver tests based on SI conventional units. ALT = Alanine Aminotransferase, AST = Aspartate Aminotransferase, ULN = Upper Limit of Normal.
• Complete Response (CR) Rate at Planned End of Therapy Based on IRRC Assessments in Cohort D [ Time Frame: From first dose to the date of initial objectively documented progression or the date of subsequent therapy, or death whichever occurred first (up to approximately 100 months) ]
  CR rate is the percent of participants who show CR (disappearance of all evidence of disease) according to the 2007 IWG criteria at the planned end of study therapy radiographic tumor assessment. Confidence interval based on the Klopper and Pearson method.

Original Secondary Outcome Measures (submitted: July 3, 2014)

• Duration of response (DOR) [ Time Frame: Up to one year after last patient first treatment ]
• Complete remission (CR) rate and duration [ Time Frame: Up to one year after last patient first treatment ]
• Partial remission (PR) rate and duration [ Time Frame: Up to one year after last patient first treatment ]
• Investigator-assessed Objective Response Rate and Duration of Response [ Time Frame: Up to one year after last patient first treatment ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Nivolumab in Patients With Classical Hodgkin's Lymphoma (Registrational)
• Official Title: Non-Comparative, Multi-Cohort, Single Arm, Open-Label, Phase 2 Study of Nivolumab (BMS-936558) in Classical Hodgkin Lymphoma (cHL) Subjects
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hodgkin Disease

Intervention

• 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

Study Arms

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

Interventions:

• Drug: Nivolumab
• Drug: Doxorubicin
• Drug: Vinblastine
• Drug: Dacarbazine

Publications *

• Cader FZ, Hu X, Goh WL, Wienand K, Ouyang J, Mandato E, Redd R, Lawton LN, Chen PH, Weirather JL, Schackmann RCJ, Li B, Ma W, Armand P, Rodig SJ, Neuberg D, Liu XS, Shipp MA. A peripheral immune signature of responsiveness to PD-1 blockade in patients with classical Hodgkin lymphoma. Nat Med. 2020 Sep;26(9):1468-1479. doi: 10.1038/s41591-020-1006-1. Epub 2020 Aug 10.
• Ramchandren R, Domingo-Domenech E, Rueda A, Trneny M, Feldman TA, Lee HJ, Provencio M, Sillaber C, Cohen JB, Savage KJ, Willenbacher W, Ligon AH, Ouyang J, Redd R, Rodig SJ, Shipp MA, Sacchi M, Sumbul A, Armand P, Ansell SM. Nivolumab for Newly Diagnosed Advanced-Stage Classic Hodgkin Lymphoma: Safety and Efficacy in the Phase II CheckMate 205 Study. J Clin Oncol. 2019 Aug 10;37(23):1997-2007. doi: 10.1200/JCO.19.00315. Epub 2019 May 21.
• Armand P, Engert A, Younes A, Fanale M, Santoro A, Zinzani PL, Timmerman JM, Collins GP, Ramchandren R, Cohen JB, De Boer JP, Kuruvilla J, Savage KJ, Trneny M, Shipp MA, Kato K, Sumbul A, Farsaci B, Ansell SM. Nivolumab for Relapsed/Refractory Classic Hodgkin Lymphoma After Failure of Autologous Hematopoietic Cell Transplantation: Extended Follow-Up of the Multicohort Single-Arm Phase II CheckMate 205 Trial. J Clin Oncol. 2018 May 10;36(14):1428-1439. doi: 10.1200/JCO.2017.76.0793. Epub 2018 Mar 27. Erratum In: J Clin Oncol. 2018 Sep 10;36(26):2748.
• Roemer MGM, Redd RA, Cader FZ, Pak CJ, Abdelrahman S, Ouyang J, Sasse S, Younes A, Fanale M, Santoro A, Zinzani PL, Timmerman J, Collins GP, Ramchandren R, Cohen JB, De Boer JP, Kuruvilla J, Savage KJ, Trneny M, Ansell S, Kato K, Farsaci B, Sumbul A, Armand P, Neuberg DS, Pinkus GS, Ligon AH, Rodig SJ, Shipp MA. Major Histocompatibility Complex Class II and Programmed Death Ligand 1 Expression Predict Outcome After Programmed Death 1 Blockade in Classic Hodgkin Lymphoma. J Clin Oncol. 2018 Apr 1;36(10):942-950. doi: 10.1200/JCO.2017.77.3994. Epub 2018 Feb 2.
• Hude I, Sasse S, Brockelmann PJ, von Tresckow B, Momotow J, Engert A, Borchmann S. Leucocyte and eosinophil counts predict progression-free survival in relapsed or refractory classical Hodgkin Lymphoma patients treated with PD1 inhibition. Br J Haematol. 2018 Jun;181(6):837-840. doi: 10.1111/bjh.14705. Epub 2017 Apr 25. No abstract available.
• Younes A, Santoro A, Shipp M, Zinzani PL, Timmerman JM, Ansell S, Armand P, Fanale M, Ratanatharathorn V, Kuruvilla J, Cohen JB, Collins G, Savage KJ, Trneny M, Kato K, Farsaci B, Parker SM, Rodig S, Roemer MG, Ligon AH, Engert A. Nivolumab for classical Hodgkin's lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial. Lancet Oncol. 2016 Sep;17(9):1283-94. doi: 10.1016/S1470-2045(16)30167-X. Epub 2016 Jul 20.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 19, 2019): 294
• Original Estimated Enrollment (submitted: July 3, 2014): 120
• Actual Study Completion Date: December 27, 2022
• Actual Primary Completion Date: August 31, 2017 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Belgium, Canada, Czechia, Germany, Italy, Netherlands, Spain, United Kingdom, United States
• Removed Location Countries: Czech Republic, France

Administrative Information

• NCT Number: NCT02181738
• Other Study ID Numbers: CA209-205; 2014-001509-42 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Bristol-Myers Squibb
• Original Responsible Party: Same as current
• Current Study Sponsor: Bristol-Myers Squibb
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

• PRS Account: Bristol-Myers Squibb
• Verification Date: November 2023