Clinical trial NCT02181738: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hodgkin Disease
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2014-07-04
Enrollment: 294
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Objective Response Rate (ORR) Based on IRRC Assessments in Cohorts A, B, and C
timeFrame: 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)
measure: Number of Participants Who Experienced at Least One Treatment Related Grade 3-5 AE in Cohort D
timeFrame: 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:
measure: Duration of Objective Response Based on IRRC Assessments in Cohorts A, B, and C
timeFrame: 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).
measure: Complete Remission (CR) Rate Based on IRRC Assessments in Cohorts A, B, and C
timeFrame: 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)
measure: Duration of Complete Remission (CR) Based on IRRC Assessments for Cohorts A, B, and C
timeFrame: 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)
measure: Partial Remission (PR) Rate Based on IRRC Assessments in Cohorts A, B, and C
timeFrame: 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)
measure: Duration of PR Based on IRRC Assessments in Cohorts A, B, and C
timeFrame: 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)
measure: Objective Response Rates (ORR) Based on Investigator Assessments for Cohorts A, B, and C
timeFrame: 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)
measure: Duration of Objective Response (DOR) Based on Investigator Assessments in Cohorts A, B, and C
timeFrame: 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)
measure: Treatment Discontinuation Rate in Cohort D
timeFrame: From first dose up until the date of treatment discontinuation (up to approximately 100 months).
measure: Number of Participants Who Died in Cohort D
timeFrame: 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)
measure: Number of Participants With Adverse Events (AEs) in Cohort D
timeFrame: 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)
measure: Number of Participants With Serious Adverse Events (SAEs) in Cohort D
timeFrame: 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)
measure: Number of Participants With AEs Leading to Discontinuation in Cohort D
timeFrame: 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)
measure: Number of Participants With AEs Leading to Dose Delay in Cohort D
timeFrame: 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)
measure: Number of Participants With Select AEs in Cohort D
timeFrame: 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)
measure: Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests in Cohort D Monotherapy Phase
timeFrame: From first dose of monotherapy to 30 days after last dose of monotherapy phase (up to approximately 3 months)
measure: Number of Participants Laboratory Abnormalities in Specific Thyroid Tests in Cohort D Combination Therapy Phase
timeFrame: 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)
measure: Number of Participants With Laboratory Abnormalities in Specific Liver Tests in Cohort D Monotherapy Phase
timeFrame: From first dose of monotherapy to 30 days after last dose of monotherapy phase (up to approximately 3 months)
measure: Number of Participants With Laboratory Abnormalities in Specific Liver Tests in Cohort D Combination Therapy Phase
timeFrame: 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)
measure: Complete Response (CR) Rate at Planned End of Therapy Based on IRRC Assessments in Cohort D
timeFrame: 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)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Local Institution - 0030
state: California
city: Los Angeles
country: United States
facility: Local Institution - 0009
state: California
city: Atlanta
country: United States
facility: Local Institution - 0001
state: Georgia
city: Boston
country: United States
facility: Local Institution - 0002
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 0025
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 0041
state: Massachusetts
city: Detroit
country: United States
facility: Local Institution - 0008
state: Michigan
city: Rochester
country: United States
facility: Local Institution - 0003
state: Minnesota
city: Hackensack
country: United States
facility: Local Institution - 0047
state: New Jersey
city: Basking Ridge
country: United States
facility: Local Institution - 0040
state: New York
city: New York
country: United States
facility: Local Institution - 0005
state: New York
city: Allentown
country: United States
facility: Local Institution - 0006
state: Pennsylvania
city: Nashville
country: United States
facility: Local Institution - 0004
state: Tennessee
city: Houston
country: United States
facility: Local Institution - 0007
state: Texas
city: Innsbruck
country: Austria
facility: Local Institution - 0032
city: Wien
country: Austria
facility: Local Institution - 0031
city: B-leuven
country: Belgium
facility: Local Institution - 0014
city: Gent
country: Belgium
facility: Local Institution - 0015
city: Vancouver
country: Canada
facility: Local Institution - 0046
state: British Columbia
city: Toronto
country: Canada
facility: Local Institution - 0042
state: Ontario
city: Praha 2
country: Czechia
facility: Local Institution - 0044
city: Berlin
country: Germany
facility: Local Institution - 0037
city: Hamburg
country: Germany
facility: Local Institution - 0036
city: Koeln
country: Germany
facility: Local Institution - 0033
city: Ulm
country: Germany
facility: Local Institution - 0034
city: Bologna
country: Italy
facility: Local Institution - 0019
city: Napoli
country: Italy
facility: Local Institution - 0020
city: Rozzano (milano)
country: Italy
facility: Local Institution - 0035
city: Amsterdam
country: Netherlands
facility: Local Institution - 0016
city: Groningen
country: Netherlands
facility: Local Institution - 0038
city: Utrecht
country: Netherlands
facility: Local Institution - 0017
city: Hospitalet Llobregat- Barcelona
country: Spain
facility: Local Institution - 0022
city: Majadahonda - Madrid
country: Spain
facility: Local Institution - 0027
city: Marbella
country: Spain
facility: Local Institution - 0023
city: Swansea
country: United Kingdom
facility: Local Institution - 0043
state: Carmarthenshire
city: Withington
country: United Kingdom
facility: Local Institution - 0012
state: Manchester
city: Oxford
country: United Kingdom
facility: Local Institution - 0026
state: Oxfordshire
city: Sutton
country: United Kingdom
facility: Local Institution - 0013
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.