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Safety Study of Anti-LAG-3 in Relapsed or Refractory Hematologic Malignancies

This study is currently recruiting participants.
See Contacts and Locations
Verified May 2017 by Bristol-Myers Squibb
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT02061761
First received: February 12, 2014
Last updated: May 15, 2017
Last verified: May 2017
  Purpose
The primary objective of this study is to characterize the safety, tolerability and maximum tolerated dose of BMS-986016 administered alone or in combination with Nivolumab to subjects with relapsed hematologic malignancies. Co-primary objective is to investigate the preliminary efficacy of BMS-986016 in combination with nivolumab in subjects with relapsed or refractory Hodgkin lymphoma (HL), and relapsed or refractory Diffuse Large B Cell lymphoma (DLBCL)

Condition Intervention Phase
Hematologic Neoplasms Biological: BMS-986016 Biological: BMS-936558 Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase 1/2a Dose Escalation and Cohort Expansion Study of the Safety, Tolerability, and Efficacy of Anti-LAG-3 (BMS-986016) in Monoclonal Antibody (BMS-986016) Administered Alone and in Combination With Anti-PD-1 Monoclonal Antibody (Nivolumab, BMS-936558) in Relapsed or Refractory B-Cell Malignancies

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Proportion of subjects with Adverse Events (AEs) [ Time Frame: Approximately 28 months ]
    Safety measured by incidence

  • Proportion of subjects with Serious Adverse Events (SAEs) [ Time Frame: Approximately 28 months ]
    Safety measured by incidence

  • Proportion of Deaths [ Time Frame: Approximately 28 months ]
    Safety measured by incidence

  • Proportion of subjects with clinical laboratory test abnormalities [ Time Frame: Approximately 28 months ]
    Safety measured by incidence

  • Objective response rate (ORR) [ Time Frame: Approximately 4 years ]
    Efficacy measured by proportion of treated subjects with a best overall response of complete response/complete remission (CR) or partial response/partial remission (PR)

  • Duration of Response (DOR) [ Time Frame: Approximately 4 years ]
    Efficacy measured by the duration of response for all treated subjects with a best overall response of CR or PR


Secondary Outcome Measures:
  • Maximum observed serum concentration (Cmax) of BMS-986016 administered alone and in combination with Nivolumab [ Time Frame: Approximately 28 months ]
    Pharmacokinetics (PK) measured by summary statistics

  • Time of maximum observed serum concentration (Tmax) of BMS-986016 administered both alone and in combination with Nivolumab [ Time Frame: Approximately 28 Months ]
    PK measured by summary statistics

  • Trough observed serum concentration (Ctrough) of BMS-986016 administered both alone and in combination with Nivolumab [ Time Frame: Approximately 28 Months ]
    PK measured by summary statistics

  • Concentration at the end of a dosing interval (Ctau) of BMS-986016 administered both alone and in combination with Nivolumab [ Time Frame: Approximately 28 Months ]
    PK measured by summary statistics

  • Average concentration over a dosing interval [AUC(TAU)/tau] (Css,avg) of BMS-986016 administered both alone and in combination with Nivolumab [ Time Frame: Approximately 28 Months ]
    PK measured by summary statistics

  • Area under the concentration-time curve in one dosing interval (AUC(TAU)) of BMS-986016 administered both alone and in combination with Nivolumab [ Time Frame: Approximately 28 Months ]
    PK measured by summary statistics

  • Total body clearance (CLT) of BMS-986016 administered both alone alone and in combination with Nivolumab [ Time Frame: Approximately 28 Months ]
    PK measured by summary statistics

  • Volume of distribution at steady state (Vss) of BMS-986016 administered both alone and in combination with Nivolumab [ Time Frame: Approximately 28 Months ]
    PK measured by summary statistics

  • Effective elimination half-life that explains the degree of AUC administered alone accumulation observed (T-HALFeff AUC) of BMS-986016 administered both alone and in combination with Nivolumab [ Time Frame: Approximately 28 Months ]
    PK measured by summary statistics

  • Effective elimination half-life that explains the degree of Cmax administered alone accumulation observed (T-HALFeff Cmax) of BMS-986016 administered both alone and in combination with Nivolumab [ Time Frame: Approximately 28 Months ]
    PK measured by summary statistics

  • Accumulation index; ration of AUC(TAU) at steady state to AUC(TAU) after the first dose (AI_AUC) of BMS-986016 administered both alone and in combination with Nivolumab [ Time Frame: Approximately 28 Months ]
    PK measured by summary statistics

  • Cmax accumulation index; ratio of Cmax at steady state to Cmax after the first dose (AI_Cmax) of BMS-986016 administered both alone and in combination with Nivolumab [ Time Frame: Approximately 28 Months ]
    PK measured by summary statistics

  • Ctau accumulation index; ratio of Ctau at steady state to Ctau after the first dose (AI_Ctau) of BMS-986016 administered both alone and in combination with Nivolumab [ Time Frame: Approximately 28 Months ]
    PK measured by summary statistics

  • Degree of fluctuation or fluctuation index ([Cmax - Ctau]/Css,avg) (DF) of BMS-986016 administered both alone and in combination with Nivolumab [ Time Frame: Approximately 28 Months ]
    PK measured by summary statistics

  • Incidence of ADA to nivolumab and BMS-986016 [ Time Frame: Approximately 28 Months ]
    Immunogenicity measured by summary statistics

  • Summary of AEs of special interest by [ Time Frame: Approximately 28 Months ]
    Immunogenicity measured by summary statistics


Estimated Enrollment: 132
Actual Study Start Date: February 25, 2014
Estimated Study Completion Date: May 15, 2020
Estimated Primary Completion Date: June 28, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BMS-986016
BMS-986016 specified dose on specified days
Biological: BMS-986016
Other Name: Anti-LAG-3 (Anti-Lymphocyte Activation Gene-3)
Experimental: BMS-986016 + BMS-936558
BMS-986-016 + BMS-936558 specified dose on specified days
Biological: BMS-986016
Other Name: Anti-LAG-3 (Anti-Lymphocyte Activation Gene-3)
Biological: BMS-936558
Other Name: Anti-PD-1 (Anti-Programmed-Death-1) ,MDX-1106 , Nivolumab

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

  • For dose escalation monotherapy: CLL, HL, NHL, MM
  • For dose expansion monotherapy: CLL, HL, NHL
  • For dose escalation and dose expansion in combination with BMS-936558: HL and DLBCL
  • Progressed, or been intolerant to, at least one standard treatment regimen
  • Not eligible for or declined transplantation or any standard therapy known to be life prolonging or life saving
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • At least 1 lesion with measurable disease at baseline
  • Availability of an existing tumor biopsy sample (or consent to allow pre-treatment tumor biopsy if sample not available)

Exclusion Criteria:

  • Known or suspected central nervous system (CNS) metastases or with the CNS as the only site of active disease (controlled CNS metastases are allowed)
  • Autoimmune disease
  • Encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent
  • Uncontrolled or significant cardiovascular disease

Other protocol defined inclusion/exclusion criteria could apply

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02061761

Contacts
Contact: Recruiting sites have contact information. Please contact the sites directly. If there is no contact information, please email: Clinical.Trials@bms.com
Contact: First line of the email MUST contain NCT# and Site #.

Locations
United States, Maryland
The Sidney Kimmel Comprehensive Cancer Center Recruiting
Baltimore, Maryland, United States, 21287
Contact: Douglas Gladstone, Site 0007    410-614-8040      
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Philippe Armand, Site 0004    617-582-8437      
United States, Michigan
Barbara Ann Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Divaya Bhutani, Site 0009    313-576-9376      
United States, Missouri
Washington University School Of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Nancy Bartlett, Site 0010    314-747-7402      
United States, New York
New York Presbyterian Hospital-Weill Cornell Med College Recruiting
New York, New York, United States, 10021
Contact: John Leonard, Site 0003    212-746-1362      
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Stephen Spurgeon, Site 0002    503-418-2086      
United States, Texas
The University Of Texas Md Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Sattva Neelapu, Site 0006    713-792-4887      
United States, Washington
Seattle Cancer Care Alliance Recruiting
Seattle, Washington, United States, 98109
Contact: Ajay Gopal, Site 0001    206-288-2037      
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02061761     History of Changes
Other Study ID Numbers: CA224-022
Study First Received: February 12, 2014
Last Updated: May 15, 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Hematologic Neoplasms
Neoplasms by Site
Neoplasms
Hematologic Diseases
Nivolumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 28, 2017