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

NCT02181738 | Completed Phase 2 Results

• 2 other identifiers: CA209-2052014-001509-42
• Study Type: interventional
• Target: 294
• Locations: 10 countries
• Sites: 38

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.

Conditions

Hodgkin Disease

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR) Based on IRRC Assessments in Cohorts A, B, and C

  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.

  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)

• Number of Participants Who Experienced at Least One Treatment Related Grade 3-5 AE in Cohort D

  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.

  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)

Secondary Outcomes (19)

• Duration of Objective Response Based on IRRC Assessments in Cohorts A, B, and C

  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).

• Complete Remission (CR) Rate Based on IRRC Assessments in Cohorts A, B, and C

  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)

• Duration of Complete Remission (CR) Based on IRRC Assessments for Cohorts A, B, and C

  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)

• Partial Remission (PR) Rate Based on IRRC Assessments in Cohorts A, B, and C

  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)

• Duration of PR Based on IRRC Assessments in Cohorts A, B, and C

  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)

Study Arms (1)

Nivolumab (Cohort A, B, C and D)

EXPERIMENTAL

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; Drug: Doxorubicin; Drug: Vinblastine; Drug: Dacarbazine

Interventions

Nivolumab DRUG

Specified dose on specified days

Also known as: BMS-936558

Nivolumab (Cohort A, B, C and D)

Doxorubicin DRUG

Specified dose on specified days

Nivolumab (Cohort A, B, C and D)

Vinblastine DRUG

Specified dose on specified days

Nivolumab (Cohort A, B, C and D)

Dacarbazine DRUG

Specified dose on specified days

Nivolumab (Cohort A, B, C and D)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (38)

Local Institution - 0030

Los Angeles, California, 90048, United States

Location

Local Institution - 0009

Los Angeles, California, 90095, United States

Location

Local Institution - 0001

Atlanta, Georgia, 30322, United States

Location

Local Institution - 0002

Boston, Massachusetts, 02215, United States

Location

Local Institution - 0025

Boston, Massachusetts, 02215, United States

Location

Local Institution - 0041

Boston, Massachusetts, 02215, United States

Location

Local Institution - 0008

Detroit, Michigan, 48201, United States

Location

Local Institution - 0003

Rochester, Minnesota, 55905, United States

Location

Local Institution - 0047

Hackensack, New Jersey, 07601, United States

Location

Local Institution - 0040

Basking Ridge, New York, 07920, United States

Location

Local Institution - 0005

New York, New York, 10021, United States

Location

Local Institution - 0006

Allentown, Pennsylvania, 18103, United States

Location

Local Institution - 0004

Nashville, Tennessee, 37232-6307, United States

Location

Local Institution - 0007

Houston, Texas, 77030, United States

Location

Local Institution - 0032

Innsbruck, 6020, Austria

Location

Local Institution - 0031

Vienna, 1090, Austria

Location

Local Institution - 0014

B-leuven, 3000, Belgium

Location

Local Institution - 0015

Ghent, 9000, Belgium

Location

Local Institution - 0046

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Local Institution - 0042

Toronto, Ontario, M5G 2M9, Canada

Location

Local Institution - 0044

Prague, 128 08, Czechia

Location

Local Institution - 0037

Berlin, 10117, Germany

Location

Local Institution - 0033

Cologne, 50937, Germany

Location

Local Institution - 0036

Hamburg, 20099, Germany

Location

Local Institution - 0034

Ulm, 89081, Germany

Location

Local Institution - 0019

Bologna, 40126, Italy

Location

Local Institution - 0020

Napoli, 80131, Italy

Location

Local Institution - 0035

Rozzano (milano), 20089, Italy

Location

Local Institution - 0016

Amsterdam, 1066 CX, Netherlands

Location

Local Institution - 0038

Groningen, 9713 GZ, Netherlands

Location

Local Institution - 0017

Utrecht, 3584 CX, Netherlands

Location

Local Institution - 0022

Hospitalet Llobregat- Barcelona, 9908, Spain

Location

Local Institution - 0027

Majadahonda - Madrid, 28222, Spain

Location

Local Institution - 0023

Marbella, 29603, Spain

Location

Local Institution - 0043

Swansea, Carmarthenshire, SA2 8QA, United Kingdom

Location

Local Institution - 0012

Withington, Manchester, M20 4BX, United Kingdom

Location

Local Institution - 0026

Oxford, Oxfordshire, OX3 7LJ, United Kingdom

Location

Local Institution - 0013

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (6)

• 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.

  PMID: 32778827 DERIVED

• 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.

  PMID: 31112476 DERIVED

• 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.

  PMID: 29584546 DERIVED

• 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.

  PMID: 29394125 DERIVED

• 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.

  PMID: 28439879 DERIVED

• 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.

  PMID: 27451390 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

MeSH Terms

Conditions

Hodgkin Disease

Interventions

Nivolumab; Doxorubicin; Vinblastine; Dacarbazine

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Bristol Myers Squibb Study Director
• Organization: Bristol Myers Squibb

Clinical.Trials@bms.com

855-907-3286

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2014
• First Posted: July 4, 2014
• Study Start: August 12, 2014
• Primary Completion: August 31, 2017
• Study Completion: December 27, 2022
• Last Updated: November 28, 2023
• Results First Posted: December 11, 2018

Record last verified: 2023-11

Locations

AU (2); CA (2); IT (3); DE (4); US (14); GB (4); BE (2); CZ (1); ES (3); NL (3)