Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Evaluate the Safety and Efficacy of Nivolumab Monotherapy and Nivolumab in Combination With Ipilimumab in Pediatric Participants With High Grade Primary Central Nervous System (CNS) Malignancies (CheckMate 908)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03130959
Recruitment Status : Completed
First Posted : April 27, 2017
Results First Posted : April 1, 2021
Last Update Posted : April 5, 2022
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Brief Summary:
The purpose of this study is to determine the safety and effectiveness of nivolumab alone and in combination with ipilimumab in pediatric patients with high grade primary central nervous system (CNS) malignancies.

Condition or disease Intervention/treatment Phase
Various Advanced Cancer Biological: Nivolumab Biological: Ipilimumab Phase 2

Expanded Access : An investigational treatment associated with this study has been approved for sale to the public.   More info ...

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 166 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase Ib /II Clinical Trial of Nivolumab Monotherapy and Nivolumab in Combination With Ipilimumab in Pediatric Subjects With High Grade Primary CNS Malignancies
Actual Study Start Date : June 12, 2017
Actual Primary Completion Date : March 10, 2020
Actual Study Completion Date : January 17, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Module A Biological: Nivolumab
Specified dose on specified days
Other Name: Opdivo, BMS-936558

Experimental: Module B Biological: Nivolumab
Specified dose on specified days
Other Name: Opdivo, BMS-936558

Biological: Ipilimumab
Specified dose on specified days
Other Name: Yervoy, BMS-734016




Primary Outcome Measures :
  1. Number of Safety Lead-In Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: up to 6 weeks post-dosing ]
    A dose-limiting toxicity (DLT) is defined as a drug-related AE occurring in the first 6 weeks of study treatment. A participant was considered evaluable for a DLT if study treatment was delayed > 2 weeks or was discontinued due to a related Adverse Event (AE), or if planned study treatment (3 doses of nivolumab in Module A, 2 doses of nivolumab plus ipilimumab in Module B) was administered and safety evaluation after 6 weeks on study is available to the study steering committee (SSC).

  2. Number of Safety Lead-In Participants With Serious Adverse Events (SAEs) [ Time Frame: up to 6 weeks post-dosing ]
    The number of Safety Lead-In Participants who experienced a Serious Adverse Event (SAE) during the course of the study.

  3. Number of Safety Lead-In Participants With Adverse Events (AEs) Leading to Discontinuation [ Time Frame: up to 6 weeks post-dosing ]
    The number of Safety Lead-In Participants who experienced an Adverse Event (AE) during the course of the study that lead to discontinuation of study therapy.

  4. Overall Survival (OS), Cohort 1 Only [ Time Frame: up to approximately 42 months ]
    Overall survival (OS) is defined as the time between the date of diagnosis and the date of death in Cohort 1.

  5. Progression-Free Survival (PFS), Cohorts 2-4 [ Time Frame: up to approximately 42 months ]
    Progression-free survival (PFS) is defined as the time from first dose to the date of the first documented tumor progression or death due to any cause.

  6. Progression-Free Survival (PFS), Cohort 5 Only [ Time Frame: up to approximately 42 months ]
    Progression-free survival (PFS) is defined as the time from first dose to the date of the first documented tumor progression or death due to any cause.


Secondary Outcome Measures :
  1. Progression-Free Survival (PFS), Cohort 1 Only [ Time Frame: up to approximately 42 months ]
    Progression-free survival (PFS) is defined as the time from first dose to the date of the first documented tumor progression or death due to any cause.

  2. Overall Survival at 12 Months (OS12), Cohorts 1-4 [ Time Frame: up to 12 months ]
    Overall survival at 12 months (OS12) is defined as the percentage of participants who are alive at 12 months, measured as the survival rate at 12 months from Kaplan-Meier product limit cumulative probability.

  3. Progression-Free Survival at 6 Months (PFS6), Cohorts 2-5 [ Time Frame: up to 6 months ]
    Progression-free survival at 6 months (PFS6) is defined as the percentage of participants who are progression free and alive at 6 months following first dose date, measured as the survival rate at 6 months from Kaplan-Meier product limit cumulative probability of progression free.

  4. Overall Survival (OS), Cohorts 2-5 [ Time Frame: up to approximately 42 months ]
    Overall survival (OS) is defined as the time between date of first dose and the date of death for Cohorts 2-5.

  5. Number of Treated Participants With Adverse Events (AEs) [ Time Frame: from first dose to 30 days post-last dose, assessed up to 13Jan2021 (up to approximately 42 months) ]
    The number of treated participants who experienced an Adverse Event (AE) during the course of the study.

  6. Number of Treated Participants With Serious Adverse Events (SAEs) [ Time Frame: from first dose to 30 days post-last dose, assessed up to 13Jan2021 (up to approximately 42 months) ]

    The number of treated participants who experienced a Serious Adverse Event (SAE) during the course of the study.

    Note: The reporting timeframe of the SAEs for this Outcome Measure (first dose to 30 days post last dose) differs than that of the reporting timeframe of the SAEs reported under the AE section of the results form (first dose to 100 days post last dose) and thus, the data in each table of SAEs reflects the specific timeframe applied.


  7. Number of Treated Participants With Drug-Related Adverse Events [ Time Frame: from first dose to 30 days post-last dose, assessed up to 13Jan2021 (up to approximately 42 months) ]
    The number of treated participants who experienced a Drug-Related Adverse Event during the course of the study.

  8. Number of Treated Participants With Adverse Events Leading to Discontinuation [ Time Frame: from first dose to 30 days post-last dose, assessed up to 13Jan2021 (up to approximately 42 months) ]
    The number of treated participants who experienced an Adverse Event leading to discontinuation during the course of the study.

  9. Number of Treated Participant Deaths [ Time Frame: from first dose assessed up to 13Jan2021 (up to approximately 42 months) ]
    The number of treated participants who died during the course of the study.

  10. Number of Treated Participant With Laboratory Abnormalities - Liver [ Time Frame: from first dose assessed up to 13Jan2021 (up to approximately 42 months) ]

    The number of treated participants who experienced a laboratory abnormality of the liver during the course of the study.

    Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Upper Limit of Normal (ULN)


  11. Number of Treated Participant With Laboratory Abnormalities - Thyroid [ Time Frame: from first dose assessed up to 13Jan2021 (up to approximately 42 months) ]

    The number of treated participants who experienced a laboratory abnormality of the thyroid during the course of the study.

    Free T3 (FT3) Free T4 (FT4) Lower Limit of Normal (LLN)




Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   6 Months to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must have received standard of care therapy, and there must be no potentially-curative treatment available, in one of the following cohorts:
  • A newly diagnosed Diffuse Intrinsic Pontine Glioma (DIPG) that has been treated with radiation therapy (RT) but no chemotherapy
  • A histologically confirmed recurrent or progressive non-brainstem High Grade Glioma (HGG) previously treated with surgical resection and RT
  • A histologically confirmed medulloblastoma that has relapsed or is resistant to at least one line of prior therapy including surgery, RT, and chemotherapy
  • A histologically confirmed ependymoma that has relapsed or is resistant to at least one line of prior therapy including surgical resection and RT
  • A histologically-confirmed high grade CNS malignancy "other than above" which is recurrent or progressive after at least one line of prior therapy
  • Lansky play score (LPS) for ≤ 16 years of age or Karnofsky performance scale (KPS) for > 16 years of age assessed within two weeks of enrollment must be >= 60
  • A tumor sample must be available for submission to central laboratory (not required for DIPG)

Exclusion Criteria:

  • An active, known, or suspected autoimmune disease
  • A concurrent condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of start of study treatment
  • Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).

Other protocol defined inclusion/exclusion criteria apply


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03130959


Locations
Show Show 54 study locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Layout table for investigator information
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  Study Documents (Full-Text)

Documents provided by Bristol-Myers Squibb:
Study Protocol  [PDF] September 11, 2017
Statistical Analysis Plan  [PDF] April 18, 2018

Additional Information:
Layout table for additonal information
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT03130959    
Other Study ID Numbers: CA209-908
2016-004441-82 ( EudraCT Number )
First Posted: April 27, 2017    Key Record Dates
Results First Posted: April 1, 2021
Last Update Posted: April 5, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms
Nivolumab
Ipilimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action