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)

July 14, 2022 updated by: Bristol-Myers Squibb

Phase Ib /II Clinical Trial of Nivolumab Monotherapy and Nivolumab in Combination With Ipilimumab in Pediatric Subjects With High Grade Primary CNS Malignancies

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
166

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Expanded Access

Expanded Access

A way for patients with serious diseases or conditions who cannot participate in a clinical trial to gain access to a medical product that has not been approved by the U.S. Food and Drug Administration (FDA). Also called compassionate use. There are different expanded access types.
Approved

Approved

  • Available: Expanded access is currently available for this investigational treatment, and patients who are not participants in the clinical study may be able to gain access to the drug, biologic, or medical device being studied.
  • No longer available: Expanded access was available for this intervention previously but is not currently available and will not be available in the future.
  • Temporarily not available: Expanded access is not currently available for this intervention but is expected to be available in the future.
  • Approved for marketing: The intervention has been approved by the U.S. Food and Drug Administration for use by the public.
 for sale to the public. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Randwick, New South Wales, Australia, 2031
        • Local Institution - 0022
    • Queensland
      • Sth Brisbane, Queensland, Australia, 4101
        • Local Institution - 0035
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Local Institution
      • Parkville, Victoria, Australia, 3052
        • Local Institution - 0034
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Local Institution - 0033
  • Brazil
      • Sao Paulo, Brazil, 04023-062
        • Local Institution - 0049
      • Sao Paulo, Brazil, 08270-070
        • Local Institution - 0050
    • RIO Grande DO SUL
      • Porto Alegre, RIO Grande DO SUL, Brazil, 90035-074
        • Local Institution - 0052
    • Sao Paulo
      • Barretos, Sao Paulo, Brazil, 14784-400
        • Local Institution - 0051
      • Ribeirao Preto, Sao Paulo, Brazil, 14048-900
        • Local Institution - 0053
  • Canada
      • Quebec, Canada, G1V 4G2
        • Local Institution - 0002
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • Local Institution - 0021
    • Quebec
      • Montreal, Quebec, Canada, H4A 3J1
        • Local Institution - 0001
  • France
      • Angers, France, 49100
        • Local Institution - 0028
      • Bordeaux Cedex, France, 33076
        • Local Institution - 0029
      • Lille, France, 59000
        • Local Institution - 0027
      • Lyon, France, 69008
        • Local Institution - 0025
      • Marseille, France, 13385 cedex 05
        • Local Institution - 0024
      • Paris, France, 75231 cedex 5
        • Local Institution - 0023
      • VIillejuif, France, 94805 CEDEX
        • Local Institution - 0026
      • Vandoeuvre les Nancy, France, 54500
        • Local Institution - 0064
  • Germany
      • Essen, Germany, 45147
        • Local Institution - 0060
      • Hamburg, Germany, 20246
        • Local Institution - 0061
      • Heidelberg, Germany, 69120
        • Local Institution - 0063
      • Wuerzburg, Germany, 97080
        • Local Institution - 0062
  • Hong Kong
      • Hong Kong, Hong Kong, 852
        • Local Institution - 0018
  • Israel
      • Haifa, Israel, 3109601
        • Local Institution - 0059
      • Ramat Gan, Israel, 5266202
        • Local Institution - 0058
  • Netherlands
      • Rotterdam, Netherlands, 3015 GJ
        • Local Institution - 0007
      • Utrecht, Netherlands, 3584 EA
        • Local Institution - 0008
  • Norway
      • Oslo, Norway, 0027
        • Local Institution - 0067
  • Poland
      • Warszawa, Poland, 04-730
        • Local Institution - 0047
  • Russian Federation
      • Moscow, Russian Federation, 117997
        • Local Institution - 0048
  • Spain
      • Esplugues de Llobregat, Spain, 08950
        • Local Institution - 0037
      • Madrid, Spain, 28009
        • Local Institution - 0038
      • Valencia, Spain, 46026
        • Local Institution - 0036
  • Sweden
      • Solna, Sweden, 171 76
        • Local Institution - 0065
  • United Kingdom
    • Greater London
      • London, Greater London, United Kingdom, WC1N 3JH
        • Local Institution - 0010
    • Merseyside
      • Liverpool, Merseyside, United Kingdom, L12 2AP
        • Local Institution - 0013
    • Tyne And Wear
      • Newcastle Upon Tyne, Tyne And Wear, United Kingdom, NEI 4LP
        • Local Institution - 0015
  • United States
    • California
      • Los Angeles, California, United States, 90027
        • Local Institution - 0057
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Local Institution - 0016
    • Florida
      • Gainesville, Florida, United States, 32611
        • Local Institution - 0046
    • Illinois
      • Chicago, Illinois, United States, 60611-2605
        • Local Institution - 0011
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Local Institution - 0005
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Local Institution - 0043
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Local Institution - 0044
    • New York
      • New York, New York, United States, 10021
        • Local Institution - 0004
      • New York, New York, United States, 10032
        • Local Institution - 0017
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Local Institution - 0066
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Local Institution
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • Local Institution - 0012
    • Texas
      • Houston, Texas, United States, 77030
        • Local Institution - 0042

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

2 years to 17 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Module A
Biological: Nivolumab
Specified dose on specified days
Other Names:
  • Opdivo, BMS-936558
Experimental: Module B
Biological: Nivolumab
Specified dose on specified days
Other Names:
  • Opdivo, BMS-936558
Biological: Ipilimumab
Specified dose on specified days
Other Names:
  • Yervoy, BMS-734016

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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).
up to 6 weeks post-dosing
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.
up to 6 weeks post-dosing
Number of Safety Lead-In Participants With Adverse Events (AEs) Leading to Discontinuation
Time Frame: From first dose to 30 days post-last dose (up to approximately 6 weeks)
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.
From first dose to 30 days post-last dose (up to approximately 6 weeks)
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.
up to approximately 42 months
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.
up to approximately 42 months
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.
up to approximately 42 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS), Cohort 1 Only
Time Frame: From first dose to the date of the first documented tumor progression or death due to any cause (up to approximately 55 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.

Progression is defined as:

  • ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement
  • Significant increase in T2 or fast fluid-attenuated inversion recovery (FLAIR) non-enhancing lesions on stable or increasing doses of corticosteroids
  • Any new lesion
  • Clear clinical deterioration not attributable to other causes apart from the tumor
  • Failure to return for evaluation as a result of death or deteriorating condition
  • Clear progression of non-measurable disease
From first dose to the date of the first documented tumor progression or death due to any cause (up to approximately 55 months)
Overall Survival at 12 Months (OS12), Cohorts 1-4
Time Frame: From first dose to up to 12 months after first dose
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.
From first dose to up to 12 months after first dose
Progression-Free Survival at 6 Months (PFS6), Cohorts 2-5
Time Frame: From first dose to up to 6 months after first dose

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.

Progression is defined as:

  • ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement
  • Significant increase in T2 or fast fluid-attenuated inversion recovery (FLAIR) non-enhancing lesions on stable or increasing doses of corticosteroids
  • Any new lesion
  • Clear clinical deterioration not attributable to other causes apart from the tumor
  • Failure to return for evaluation as a result of death or deteriorating condition
  • Clear progression of non-measurable disease
From first dose to up to 6 months after first dose
Overall Survival (OS), Cohorts 2-5
Time Frame: From first dose to the date of death (up to approximately 55 months)
Overall survival (OS) is defined as the time between date of first dose and the date of death for Cohorts 2-5.
From first dose to the date of death (up to approximately 55 months)
Number of Treated Participants With Adverse Events (AEs)
Time Frame: From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months)

The number of treated participants who experienced an Adverse Event (AE) during the course of the study.

An 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.
From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months)
Number of Treated Participants With Serious Adverse Events (SAEs)
Time Frame: From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months)

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

SAE is defined as any untoward medical occurrence that, at any dose:

  • Results in death
  • Is life-threatening
  • 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

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.
From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months)
Number of Treated Participants With Drug-Related Adverse Events
Time Frame: From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months)

The number of treated participants who experienced a Drug-Related Adverse Event during the course of the study.

An 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.
From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months)
Number of Treated Participants With Adverse Events Leading to Discontinuation
Time Frame: From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months)

The number of treated participants who experienced an Adverse Event leading to discontinuation during the course of the study.

An 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.
From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months)
Number of Treated Participant Deaths
Time Frame: From first dose to the date of death (up to approximately 55 months)
The number of treated participants who died during the course of the study.
From first dose to the date of death (up to approximately 55 months)
Number of Treated Participant With Laboratory Abnormalities - Liver
Time Frame: From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 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) Units per Liter (U/L) Results reported in International System of Units (SI)
From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months)
Number of Treated Participant With Laboratory Abnormalities - Thyroid
Time Frame: From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 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) Thyroid stimulating hormone (TSH) Lower Limit of Normal (LLN) Upper limit of normal (ULN) Milliunits per Liter (mlU/L) Results reported in International System of Units (SI)
From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Bristol-Myers Squibb

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 12, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 10, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 17, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 5, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 24, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 27, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 9, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 14, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CA209-908
  • 2016-004441-82 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Various Advanced Cancer

Clinical Trials on Nivolumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings