Hodgkin's DiseasePhase 3CheckMate 812NCT03138499

A Study of Nivolumab Plus Brentuximab Vedotin Versus Brentuximab Vedotin Alone in Patients With Advanced Stage Classical Hodgkin Lymphoma, Who Are Relapsed/ Refractory or Who Are Not Eligible for Autologous Stem Cell Transplant,

A Phase 3 study testing Nivolumab and Brentuximab vedotin in people with Hodgkin's Disease, run by Bristol-Myers Squibb at 22 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: 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: 23 participants
Where: 22 sitesin 3 countries
Study dates: 26 Jun 2017to 22 Feb 2021
Phase: Phase 3
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 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
Participants must have a pathologic diagnosis of classical Hodgkin lymphoma (cHL) who are relapsed or refractory with one of the following:.
Autologous stem cell transplant (ASCT) ineligible patients.
Patients after failure of ASCT.
Must have at least one lesion that is > 15 mm (1.5 cm) in the longest diameter and avid by Fluoro Deoxy Glucose (FDG) Positron Emission Tomography (PET) scan.

Who cannot join

Known central nervous system lymphoma.
Participants with nodular lymphocyte-predominant Hodgkin lymphoma (HL).
Participants with known history of pancreatitis or progressive multifocal leukoencephalopathy (PML).
Other protocol-defined Inclusion/Exclusion criteria apply.

Trial locations and contacts

22 sites in 3 countries.

Country

City, postcode or hospital

22 sites in 3 countries

United States20 sites

Dana Farber/Harvard Cancer Center
Boston, Massachusetts, 02215
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Karmanos Cancer Institute
Detroit, Michigan, 48201
City of Hope National Medical Center
Duarte, California, 91010
Parkview Cancer Center
Fort Wayne, Indiana, 46845
Bon Secours Saint Francis Cancer Center
Greenville, South Carolina, 29607
The University of Texas MD Anderson Cancer Center-merge
Houston, Texas, 77030
Pacific Shores Medical Group
Long Beach, California, 90813
University of Southern California
Los Angeles, California, 90033
UCLA Clinical and Translational Research Center (CTRC)
Los Angeles, California, 90095-1678
Vanderbilt Ingram Cancer Center
Nashville, Tennessee, 37213
Tulane University Health Sciences Center
New Orleans, Louisiana, 70112
Orlando Health, Inc
Orlando, Florida, 32806
Local Institution
Palo Alto, California, 94304
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Hartford Healthcare Cancer Institute at the Hospital of Central Connecticut
Plainville, Connecticut, 06062
UC Davis Comprehensive Cancer Center
Sacramento, California, 95817
University of California San Diego
San Diego, California, 92122
University of Kansas Cancer Center
Westwood, Kansas, 66205
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157

Other trials in United States

Japan1 site

Local Institution
Sendai, Miyagi, 9808574

Other trials in Japan

Puerto Rico1 site

Local Institution
San Juan, 00918

Other trials in Puerto Rico

About this study

Official title: Randomized, Open-label, Phase 3 Trial of Nivolumab Plus Brentuximab Vedotin Versus Brentuximab Vedotin Alone in Participants With Relapsed Refractory or Ineligible for Autologous Stem Cell Transplant (ASCT) Advanced Stage Classical Hodgkin Lymphoma (CheckMate 812: CHECKpoint Pathway and nivoluMAb Clinical Trial Evaluation 812)

The purpose of this study is to determine whether an investigational immuno-therapy combination, nivolumab with Brentuximab vedotin compared to Brentuximab vedotin alone is safe and effective in the treatment of relapsed and refractory Classical Hodgkin Lymphoma. The participants of this trial will comprise of patients who have relapsed or did not respond to treatment and are not eligible for stem cell transplant

Conditions: Hodgkin's Disease
Being tested: Nivolumab, Brentuximab vedotin
Medical subject headings: Hodgkin Disease

What participants receive

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

NivolumabBiological
Also called Opdivo
Specified dose on specified days
Brentuximab vedotinBiological
Also called Adcetris
Specified dose on specified days

Study groups in NCT03138499
Study group	Role	What they receive
Module A	Experimental	Nivolumab combined with Brentuximab Receives: Biological: Nivolumab; Biological: Brentuximab vedotin
Module B	Experimental	Brentuximab alone Receives: Biological: Brentuximab vedotin

What is being measured

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

Progression Free Survival (PFS)
Progression Free Survival (PFS) is defined as time from date of randomization to death, or disease progression per investigator assessment estimated using the Kaplan-Meier (KM) product-limit method.
Measured: From randomization to date of death, or disease progression (up to approximately 45 months)

Secondary outcomes (5)

Complete Response Rate (CRR):
Complete Response Rate (CRR) is defined as the number of participants who have achieved complete response (Lugano 2014 classification) per investigator assessment. Complete response is considered a score of 1, 2, or 3.
Per the Lugano criteria:
Positron emission tomography (PET) negative scans are defined on the 5-point scale as scores of 1, 2, or 3 (where 1 = no uptake above background; 2 = uptake </= mediastinum; and 3 = uptake > mediastinum but </= liver) and PET-positive scans, as scores of 4 or 5 (where 4 = uptake moderately higher than liver; 5 = uptake markedly higher than liver and/or new lesions). Response on PET scans should be reported as complete metabolic response (CMR) partial metabolic response (PMR), SMD (stable metabolic disease), or PMD (progressive metabolic disease).
Measured: From randomization up to approximately 45 months
Objective Response Rate (ORR)
Objective Response Rate (ORR) is defined as the number of participants with a Best Overall Response (BOR) of complete response (CR) or partial response (PR) (Lugano 2014 classification) per investigator assessment. Complete response is considered a score of 1, 2, or 3. Partial response is considered a score of 4 or 5.
Per the Lugano criteria:
Positron emission tomography (PET) negative scans are defined on the 5-point scale as scores of 1, 2, or 3 (where 1 = no uptake above background; 2 = uptake </= mediastinum; and 3 = uptake > mediastinum but </= liver) and PET-positive scans, as scores of 4 or 5 (where 4 = uptake moderately higher than liver; 5 = uptake markedly higher than liver and/or new lesions). Response on PET scans should be reported as complete metabolic response (CMR) partial metabolic response (PMR), SMD (stable metabolic disease), or PMD (progressive metabolic disease).
Measured: From randomization up to approximately 45 months
Duration of Response (DOR)
The time from first response (Complete response (CR) or partial response (PR)) to the date of initial objectively documented progression (2014 Lugano classification) or death due to any cause per investigator assessment estimated using the Kaplan-Meier (KM) product-limit method. Complete response is considered a score of 1, 2, or 3. Partial response is considered a score of 4 or 5.
Per the Lugano criteria:
Positron emission tomography (PET) negative scans are defined on the 5-point scale as scores of 1, 2, or 3 (where 1 = no uptake above background; 2 = uptake </= mediastinum; and 3 = uptake > mediastinum but </= liver) and PET-positive scans, as scores of 4 or 5 (where 4 = uptake moderately higher than liver; 5 = uptake markedly higher than liver and/or new lesions). Response on PET scans should be reported as complete metabolic response (CMR) partial metabolic response (PMR), SMD (stable metabolic disease), or PMD (progressive metabolic disease).
Measured: From randomization to date of documented progression or death (up to approximately 45 months)
Duration of Complete Response (DOCR)
Duration of complete response (DOR) is defined as the time from first complete response to the date of initial objectively documented progression (2014 Lugano classification) or death due to any cause per investigator assessment estimated using the Kaplan-Meier (KM) product-limit method. Complete response is considered a score of 1, 2, or 3.
Per the Lugano criteria:
Positron emission tomography (PET) negative scans are defined on the 5-point scale as scores of 1, 2, or 3 (where 1 = no uptake above background; 2 = uptake </= mediastinum; and 3 = uptake > mediastinum but </= liver) and PET-positive scans, as scores of 4 or 5 (where 4 = uptake moderately higher than liver; 5 = uptake markedly higher than liver and/or new lesions). Response on PET scans should be reported as complete metabolic response (CMR) partial metabolic response (PMR), SMD (stable metabolic disease), or PMD (progressive metabolic disease).
Measured: From randomization to date of documented progression or death (up to approximately 45 months)
Overall Survival (OS)
Overall Survival (OS) is defined as the time between the date of randomization and the date of death estimated using the Kaplan-Meier (KM) product-limit method
Measured: From randomization to the date of death (up to approximately 3 years 7 months)

Timeline

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

26 Jun 201722 Feb 2021

First posted3 May 2017
Study start26 Jun 2017
Primary completion22 Feb 2021
Study completion22 Feb 2021

Why it stopped: Insufficient enrollment.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Hodgkin's DiseaseStudies of the same condition, open and under way.
More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 23 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03138499
Sponsor's protocol ID: CA209-812
Other IDs: 2017-000847-41, 2017
Acronym: CheckMate 812
Status last verified: Jan 2024
First submitted: 1 May 2017
Last updated: 10 Jan 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 2
Ibrutinib Combination Therapy in Transplant Ineligible Individuals With Newly Diagnosed Primary CNS Lymphoma
Non-hodgkin Lymphoma
Active, not recruitingPhase 2
Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With CD30-Positive Peripheral T-cell Lymphoma
Adult T-Cell Leukemia/Lymphoma, Anaplastic Large Cell Lymphoma, ALK-Negative
Not yet recruitingPhase 2
Obesity Treatment With Phentermine-Topiramate ER in AYA Surviving Leukemia and Lymphoma
Acute Lymphoblastic Leukemia in Remission, Hodgkin Lymphoma in Remission
Active, not recruitingPhase 2
A Study of Anakinra to Prevent or Treat Severe Side Effects for Patients Receiving CAR-T Cell Therapy
B Cell ALL, B-Cell Lymphoma
Active, not recruitingPhase 1
A Rollover Study of CC-122
Non-Hodgkin Lymphoma

All Hodgkin's Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 10 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Randomized, Open-label, Phase 3 Trial of Nivolumab Plus Brentuximab Vedotin Versus Brentuximab Vedotin Alone in Participants With Relapsed Refractory or Ineligible for Autologous Stem Cell Transplant (ASCT) Advanced Stage Classical Hodgkin Lymphoma (CheckMate 812: CHECKpoint Pathway and nivoluMAb Clinical Trial Evaluation 812)
ClinicalTrials.gov ID: NCT03138499
Acronym / sponsor ID: CheckMate 812 / CA209-812
Conditions: Hodgkin's Disease
Phase: Phase 3
Study type: Interventional
Recruitment status: TerminatedReason stopped: Insufficient enrollment.
Enrolment: 23 participants (actual)
Lead sponsor: Bristol-Myers SquibbIndustry (pharma, biotech, devices)
Collaborators: Seagen Inc., Ono Pharmaceutical Co., Ltd.
Study start: 26 Jun 2017 (actual)
Primary completion: 22 Feb 2021 (actual)
Study completion: 22 Feb 2021 (actual)
First posted: 3 May 2017 (actual)
Results: Posted 12 Apr 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Module A	Experimental	Biological: Nivolumab, Biological: Brentuximab vedotinNivolumab combined with Brentuximab
Module B	Experimental	Biological: Brentuximab vedotinBrentuximab alone

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
Participants must have a pathologic diagnosis of classical Hodgkin lymphoma (cHL) who are relapsed or refractory with one of the following:.
Patients after failure of ASCT.
Must have at least one lesion that is > 15 mm (1.5 cm) in the longest diameter and avid by Fluoro Deoxy Glucose (FDG) Positron Emission Tomography (PET) scan.

Key exclusion criteria (4 listed)

Known central nervous system lymphoma.
Participants with nodular lymphocyte-predominant Hodgkin lymphoma (HL).
Participants with known history of pancreatitis or progressive multifocal leukoencephalopathy (PML).
Other protocol-defined Inclusion/Exclusion criteria apply.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
NivolumabAlso: OpdivoSpecified dose on specified days	Biological	Module A
Brentuximab vedotinAlso: AdcetrisSpecified dose on specified days	Biological	Module A, Module B

Primary outcome

Progression Free Survival (PFS)
Time frame: From randomization to date of death, or disease progression (up to approximately 45 months)
Progression Free Survival (PFS) is defined as time from date of randomization to death, or disease progression per investigator assessment estimated using the Kaplan-Meier (KM) product-limit method.

5 secondary outcomes

Complete Response Rate (CRR):
Time frame: From randomization up to approximately 45 months
Objective Response Rate (ORR)
Time frame: From randomization up to approximately 45 months
Duration of Response (DOR)
Time frame: From randomization to date of documented progression or death (up to approximately 45 months)
Duration of Complete Response (DOCR)
Time frame: From randomization to date of documented progression or death (up to approximately 45 months)
Overall Survival (OS)
Time frame: From randomization to the date of death (up to approximately 3 years 7 months)

Results and safety

Results posted to the registry on 12 Apr 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Nivolumab + Brentuximab Vedotin (BV)	12	3
Brentuximab Vedotin (BV)	11	1

Primary outcome: Progression Free Survival (PFS)

Time frame: From randomization to date of death, or disease progression (up to approximately 45 months). Median (95% Confidence Interval). Unit: Months

Measure	Nivolumab + Brentuximab Vedotin (BV) n = 12	Brentuximab Vedotin (BV) n = 11
Value	14.32 (10.12 to NA)	7.93 (2.86 to NA)

Population analysed: All randomized participants

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: From first dose to up to 100 days post last dose (up to approximately 2 years) All-cause mortality was assessed from date of first dose to study completion (up to approximately 3 years 7 months). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Nivolumab + Brentuximab Vedotin (BV)	6 of 12 (50%)	12 of 12 (100%)	1 of 12
Brentuximab Vedotin (BV)	1 of 10 (10%)	10 of 10 (100%)	0 of 10

Limitations and caveats (from the sponsor): Due to a treatment paradigm shift and subsequent low enrollment, the Sponsor chose to terminate the study and consequently there is limited data. These reasons were unrelated to any adverse events (AEs) or safety concerns. The sample size was smaller than expected, therefore, results should be interpreted with caution. PFS, CRR, and ORR outcomes should be interpreted with caution given large confidence intervals around medians and early study closure.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
BMS Clinical Trial InformationLink provided by the sponsor.
BMS Clinical Trial Patient RecruitingLink provided by the sponsor.
Investigator Inquiry FormLink provided by the sponsor.
FDA Safety Alerts and RecallsLink provided by the sponsor.

Related trials for Hodgkin's Disease

RecruitingPhase 2
Ibrutinib Combination Therapy in Transplant Ineligible Individuals With Newly Diagnosed Primary CNS Lymphoma
Non-hodgkin Lymphoma
Active, not recruitingPhase 2
Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With CD30-Positive Peripheral T-cell Lymphoma
Adult T-Cell Leukemia/Lymphoma, Anaplastic Large Cell Lymphoma, ALK-Negative
Not yet recruitingPhase 2
Obesity Treatment With Phentermine-Topiramate ER in AYA Surviving Leukemia and Lymphoma
Acute Lymphoblastic Leukemia in Remission, Hodgkin Lymphoma in Remission
Active, not recruitingPhase 2
A Study of Anakinra to Prevent or Treat Severe Side Effects for Patients Receiving CAR-T Cell Therapy
B Cell ALL, B-Cell Lymphoma
Active, not recruitingPhase 1
A Rollover Study of CC-122
Non-Hodgkin Lymphoma

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Bristol-Myers Squibb study director

Bristol-Myers Squibb

22 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Nivolumab and Brentuximab vedotin in people with Hodgkin's Disease, run by Bristol-Myers Squibb at 22 sites in 3 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 5 inclusion and 4 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: stopped early, as of the sponsor's last update on 10 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in United States, Japan, Puerto Rico. 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 phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 12 Apr 2022). 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?

Progression Free Survival (PFS) (time frame: From randomization to date of death, or disease progression (up to approximately 45 months)). 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 NCT03138499.

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 10 Jan 2024.