An Investigational Immuno-therapy Safety and Effectiveness Study of Nivolumab in Combination With Brentuximab Vedotin to Treat Non-Hodgkin Lymphomas

NCT02581631 | Completed Phase 1 Results

• 2 other identifiers: CA209-4362015-003286-28
• Study Type: interventional
• Target: 145
• Locations: 6 countries
• Sites: 27

Brief Summary

The purpose of this study is to determine whether Nivolumab, in combination with brentuximab vedotin, is safe and effective in patients with certain subtypes of non-Hodgkin's lymphomas with CD30 expression that have not responded to treatment or have come back. The subtypes we are studying are Diffuse Large B-Cell Lymphoma (DLBCL), Peripheral T-Cell Lymphoma (PTCL), Cutaneous T-Cell Lymphoma (CTCL), Primary Mediastinal Large B-Cell Lymphoma (PMBL) and Mediastinal Gray Zone Lymphoma (MGZL).

Conditions

Non-Hodgkin's Disease

Outcome Measures

Primary Outcomes (10)

• Safety Analysis - Number of Participants With Dose Limiting Toxicities (DLT) in the DLT Evaluation Phase

  DLTs are defined as any study drug-related toxicity (brentuximab vedotin or nivolumab) that requires either a dose reduction or delay of more than 7 days of either study drug in Cycle 2 or delays the Cycle 3 Day 1 administration of combined treatment by more than 7 days.

  From first dose of treatment to 6 weeks after first dose

• Safety Analysis - Number of Participant Deaths

  Number of participant Deaths

  CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months

• Safety Analysis - Number of Participants With Adverse Advents

  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.

  CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months

• Safety Analysis - Number of Participants With Serious Adverse Events

  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. * results in persistent or significant disability/incapacity * is a congenital anomaly/birth defect * is an important medical event

  CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months

• Safety Analysis - Number of Participants With Adverse Events Leading to Discontinuation

  Number of participants with adverse events leading to discontinuation

  CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months

• Safety Analysis - Number of Participants With Adverse Events Leading to Dose Delay or Reduction

  Number of participants with adverse events leading to dose delay or reduction

  CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months

• Safety Analysis - Number of Participants With Drug Related Adverse Events

  Number of participants with Drug Related Adverse Events

  CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months

• Safety Analysis - Percentage of Participants With Thyroid Test Abnormalities

  Percentage of participants with specific thyroid test abnormalities

  CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months

• Safety Analysis - Percentage of Participants With Liver Test Abnormalities

  Percentage of participants with specific Liver test abnormalities

  CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months

• Objective Response Rate (ORR)

  The percentage of participants with a best overall response (BOR) of CR or PR. DLBCL, PTCL, PMBL \& MGZL complete and partial response are outlined in the Lugano Classification 2014 and Lymphoma Response to Immunomodulatory therapy Criteria. CTCL complete and partial response are defined in The consensus Global Response Score assessment.

  CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months

Secondary Outcomes (5)

• Duration of Response (DOR)

  From the first patient first visit to 8 months after the last patient first visit (up to 48 months)

• Complete Response Rate (CRR)

  From first dose to the date of initial objectively documented progression or the date of subsequent therapy, whichever occurs first (up to 48 months)

• Duration of Complete Response

  From first dose to the date of relapse or death due to any cause, whichever occurs first. (about 48 months)

• Progression Free Survival (PFS)

  From first dose of study drug until the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death due to any cause, whichever comes first. (about 48 months)

• Overall Survival (OS)

  From the first patient first visit to 8 months after the last patient first visit (about 48 months)

Study Arms (1)

Nivolumab+Brentuximab Vedotin

EXPERIMENTAL

Nivolumab+Brentuximab Vedotin dose as specified

Biological: Nivolumab; Drug: Brentuximab Vedotin

Interventions

Nivolumab BIOLOGICAL

Nivolumab+Brentuximab Vedotin

Brentuximab Vedotin DRUG

Nivolumab+Brentuximab Vedotin

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Relapsed/refractory diffuse large B cell lymphoma (DLBCL), relapsed/refractory peripheral T cell lymphoma (PTCL) (all subtypes excluding anaplastic large cell lymphoma), relapsed/refractory Cutaneous T cell lymphoma (CTCL) mycosis fungoides/sezary syndrome (MF/SS), relapsed/refractory primary mediastinal B lymphoma (PMBL), and relapsed/refractory mediastinal gray zone lymphoma (MGZL)
• Expression of CD30
• Subjects must be 18 years or older (≥ 15 years for PMBL)

You may not qualify if:

• Known central nervous system (CNS) lymphomas; Active cerebral/meningeal disease related to the underlying malignancy
• Active, known, or suspected autoimmune disease

Sponsors & Collaborators

• Bristol-Myers Squibb: lead
• Seagen Inc.: collaborator

Study Sites (27)

Local Institution - 0017

Birmingham, Alabama, 35294-3300, United States

Location

University Of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Local Institution - 0012

Tampa, Florida, 33612, United States

Location

Winship Cancer Institute.

Atlanta, Georgia, 30322, United States

Location

University Of Chicago

Chicago, Illinois, 60637, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School Of Medicine

St Louis, Missouri, 63110, United States

Location

Local Institution - 0003

New York, New York, 10021, United States

Location

Local Institution - 0010

New York, New York, 10029, United States

Location

University Of Rochester

Rochester, New York, 14642, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

Bon Secours-St Francis Hosp

Greenville, South Carolina, 29607, United States

Location

University of Washington - Seattle Cancer Care Alliance

Seattle, Washington, 98109-1023, United States

Location

BC Cancer Agency - Vancouver Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Local Institution - 0011

Toronto, Ontario, M5G 2M9, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Hopital Saint Louis

Paris, 75010, France

Location

Local Institution - 0020

Pierre-Bénite, 69495, France

Location

Local Institution - 0018

Bergamo, 0, Italy

Location

Local Institution - 0024

Bologna, 40126, Italy

Location

Istituto Clinico Humanitas

Rozzano (milano), 20089, Italy

Location

Local Institution - 0027

Hospitalet de Llobregat - Barcelona, 08908, Spain

Location

Churchill Hospital

Oxford, Oxfordshire, OX3 7LJ, United Kingdom

Location

Royal Marsden Hospital

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Related Publications (2)

• Zinzani PL, Santoro A, Gritti G, Brice P, Barr PM, Kuruvilla J, Cunningham D, Kline J, Johnson NA, Mehta-Shah N, Lisano J, Wen R, Akyol A, Moskowitz AJ. Nivolumab combined with brentuximab vedotin for R/R primary mediastinal large B-cell lymphoma: a 3-year follow-up. Blood Adv. 2023 Sep 26;7(18):5272-5280. doi: 10.1182/bloodadvances.2023010254.

  PMID: 37352266 DERIVED

• Zinzani PL, Santoro A, Gritti G, Brice P, Barr PM, Kuruvilla J, Cunningham D, Kline J, Johnson NA, Mehta-Shah N, Manley T, Francis S, Sharma M, Moskowitz AJ. Nivolumab Combined With Brentuximab Vedotin for Relapsed/Refractory Primary Mediastinal Large B-Cell Lymphoma: Efficacy and Safety From the Phase II CheckMate 436 Study. J Clin Oncol. 2019 Nov 20;37(33):3081-3089. doi: 10.1200/JCO.19.01492. Epub 2019 Aug 9.

  PMID: 31398081 DERIVED

Related Links

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

MeSH Terms

Interventions

Nivolumab; Brentuximab Vedotin

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Oligopeptides; Peptides

Results Point of Contact

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

Clinical.Trials@bms.com

Please Email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2015
• First Posted: October 21, 2015
• Study Start: February 11, 2016
• Primary Completion: January 16, 2020
• Study Completion: February 7, 2022
• Last Updated: March 7, 2023
• Results First Posted: March 7, 2023

Record last verified: 2023-02

Locations

US (16); CA (3); ES (1); GB (2); IT (3); FR (2)