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Non-Hodgkin's DiseasePhase 1/2CheckMate 436NCT02581631

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

A Phase 1/2 study testing Nivolumab and Brentuximab Vedotin in people with Non-Hodgkin's Disease, run by Bristol-Myers Squibb at 27 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 15 years and older
Conditions the study is for
Non-Hodgkin's Disease
What is being tested?
Nivolumab and Brentuximab Vedotin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
145 participants
Where
27 sitesin 6 countries
Study dates
11 Feb 2016to 7 Feb 2022
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 15 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

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

Trial locations and contacts

27 sites in 6 countries.

27 sites in 6 countries

United States16 sites

  • Winship Cancer Institute.

    Atlanta, Georgia, 30322

  • Local Institution - 0017

    Birmingham, Alabama, 35294-3300

  • Levine Cancer Institute

    Charlotte, North Carolina, 28204

  • University Of Chicago

    Chicago, Illinois, 60637

  • The Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Bon Secours-St Francis Hosp

    Greenville, South Carolina, 29607

  • University Of Miami Sylvester Comprehensive Cancer Center

    Miami, Florida, 33136

  • Local Institution - 0003

    New York, New York, 10021

  • Local Institution - 0010

    New York, New York, 10029

  • Stephenson Cancer Center

    Oklahoma City, Oklahoma, 73104

  • Providence Portland Medical Center

    Portland, Oregon, 97213

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University Of Rochester

    Rochester, New York, 14642

  • University of Washington - Seattle Cancer Care Alliance

    Seattle, Washington, 98109-1023

  • Washington University School Of Medicine

    St Louis, Missouri, 63110

  • Local Institution - 0012

    Tampa, Florida, 33612

Other trials in United States

Canada3 sites

  • Jewish General Hospital

    Montreal, Quebec, H3T 1E2

  • Local Institution - 0011

    Toronto, Ontario, M5G 2M9

  • BC Cancer Agency - Vancouver Centre

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

Italy3 sites

  • Local Institution - 0018

    Bergamo, 0

  • Local Institution - 0024

    Bologna, 40126

  • Istituto Clinico Humanitas

    Rozzano (milano), 20089

Other trials in Italy

France2 sites

  • Hopital Saint Louis

    Paris, 75010

  • Local Institution - 0020

    Pierre-Bénite, 69495

Other trials in France

United Kingdom2 sites

  • Churchill Hospital

    Oxford, Oxfordshire, OX3 7LJ

  • Royal Marsden Hospital

    Sutton, Surrey, SM2 5PT

Other trials in United Kingdom

Spain1 site

  • Local Institution - 0027

    Hospitalet de Llobregat - Barcelona, 08908

Other trials in Spain

About this study

Official title: A Phase I/ II Study to Evaluate the Safety and Preliminary Efficacy of Nivolumab in Combination With Brentuximab Vedotin in Subjects With Relapsed Refractory Non Hodgkin Lymphomas With CD30 Expression (CheckMate 436: CHECKpoint Pathway and Nivolumab Clinical Trial Evaluation 436)

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).

Being tested
Nivolumab, Brentuximab Vedotin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02581631
Study groupRoleWhat they receive
Nivolumab+Brentuximab VedotinExperimentalNivolumab+Brentuximab Vedotin dose as specified
Receives: Biological: Nivolumab; Drug: Brentuximab Vedotin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: From first dose of treatment to 6 weeks after first dose

  2. Safety Analysis - Number of Participant Deaths

    Number of participant Deaths

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

  3. 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.

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

  4. 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

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

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

    Number of participants with adverse events leading to discontinuation

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

  6. 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

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

  7. Safety Analysis - Number of Participants With Drug Related Adverse Events

    Number of participants with Drug Related Adverse Events

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

  8. Safety Analysis - Percentage of Participants With Thyroid Test Abnormalities

    Percentage of participants with specific thyroid test abnormalities

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

  9. Safety Analysis - Percentage of Participants With Liver Test Abnormalities

    Percentage of participants with specific Liver test abnormalities

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

  10. 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.

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

Secondary outcomes (5)

  1. Duration of Response (DOR)

    DOR will be calculated from the date of initial documentation of a response (CR, or PR) to 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 occurs first.

    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.

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

  2. Complete Response Rate (CRR)

    The CRR is defined as the percentage of participants with a BOR (Best overall response) of CR divided by the number of treated participants.

    DLBCL, PTCL, PMBL \& MGZL (CR)

    1.Complete disappearance of all detectable clinical evidence of disease. 2.Bone marrow: No evidence of FDG- avid disease in marrow. CTCL (CR)

    1. 100% clearance of skin lesions.
    2. all lymph nodes ≤1.5 cm, N3 classification and ≤ 1.5 cm in their long axis and > 1 cm in their short axis at baseline, must be ≤ 1 cm in their short axis or biopsy negative for lymphoma.
    3. organs should not be enlarged on examination or imaging
    4. absence of blood involvement

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

  3. Duration of Complete Response

    The duration of CR will only be evaluated in participants with BOR of CR and is defined as the time from first documentation of CR to the date of relapse or death due to any cause, whichever occurs first.

    DLBCL, PTCL, PMBL \& MGZL (CR)

    1.Complete disappearance of all detectable clinical evidence of disease. 2.Bone marrow: No evidence of FDG- avid disease in marrow. CTCL (CR)

    1. 100% clearance of skin lesions.
    2. all lymph nodes ≤1.5 cm, N3 classification and ≤ 1.5 cm in their long axis and > 1 cm in their short axis at baseline, must be ≤ 1 cm in their short axis or biopsy negative for lymphoma.
    3. organs should not be enlarged on examination or imaging
    4. absence of blood involvement

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

  4. Progression Free Survival (PFS)

    PFS is defined as the time from the date of 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. Participants who are progression-free and alive or have unknown status will be censored at the last tumor assessment. Participants who did not have any onstudy tumor assessments and did not die will be censored on the date of first treatment. For participants who received subsequent therapy prior to documented progression, it will be censored on the last tumor assessment date prior to or on subsequent therapy.

    Measured: 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)

  5. Overall Survival (OS)

    OS is defined as the time from the date of first dose of study drug until the date of death (any reason). If the participant is alive or the vital status is unknown, the participant will be censored at the date the participant was last known to be alive.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Oct 2015 (estimated)
  2. Study start11 Feb 2016
  3. Primary completion16 Jan 2020
  4. Study completion7 Feb 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
145 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02581631
Sponsor's protocol ID
CA209-436
Other IDs
2015-003286-28, 2015
Acronym
CheckMate 436
Status last verified
Feb 2023
First submitted
13 Oct 2015
Last updated
7 Mar 2023
Data monitoring committee
No

Publications

  • 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.

    PubMed 37352266

  • 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.

    PubMed 31398081

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Nivolumab and Brentuximab Vedotin in people with Non-Hodgkin's Disease, run by Bristol-Myers Squibb at 27 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites in United States, Canada, Italy, France, United Kingdom and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety Analysis - Number of Participants With Dose Limiting Toxicities (DLT) in the DLT Evaluation Phase (time frame: From first dose of treatment to 6 weeks after first dose). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02581631, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Mar 2023.

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