Nivolumab With or Without Varlilumab in Treating Patients With Relapsed or Refractory Aggressive B-cell Lymphomas
A Randomized Phase 2 Study of CDX-1127 (Varlilumab) in Combination With Nivolumab in Patients With Relapsed or Refractory Aggressive B-cell Lymphomas
5 other identifiers
interventional
54
1 country
33
Brief Summary
This phase II trial studies how well nivolumab with or without varlilumab works in treating patients with aggressive B-cell lymphomas that have come back (recurrent) or do not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as varlilumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Dec 2018
Longer than P75 for phase_2
33 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 31, 2017
CompletedFirst Posted
Study publicly available on registry
February 1, 2017
CompletedStudy Start
First participant enrolled
December 21, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 26, 2023
CompletedResults Posted
Study results publicly available
October 16, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
October 24, 2026
ExpectedNovember 10, 2025
October 1, 2025
4.4 years
January 31, 2017
May 29, 2024
October 25, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Overall Response Rate
Will be assessed by computed tomography (CT)-based criteria or positron emission tomography (PET)-CT based criteria. A response will be defined as an objective status of partial remission (PR) or complete remission (CR) for patients evaluated by CT-based criteria and complete metabolic response (CMR) or partial metabolic response (PMR) for patients evaluated by PET-CT based criteria. Exact binomial ninety-five percent confidence intervals for the true success proportion will be calculated in each arm. Comparison of overall response rates between the two treatment groups will be performed using a one-sided Fisher's exact test at significance level 0.15.
2 years
Secondary Outcomes (4)
Duration of Response
2 years
Overall Survival
37 months
Progression Free Survival (PFS)
37 months
Proportion of Patients With Grade 3 or Higher Adverse Events
25 months
Other Outcomes (6)
Change in CD27 Expression in Tissue
Baseline up to 100 days after last dose of study drug
Change in Peripheral Blood Immune Cells
Baseline up to 12 weeks
Change in the Identification/Characterization of Intratumoral Immune Cells in Tissue
Baseline up to time of disease progression
- +3 more other outcomes
Study Arms (2)
Group I (nivolumab)
ACTIVE COMPARATORPatients receive nivolumab IV over 30 minutes every 2 weeks for 4 months and every 4 weeks for a total of up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may cross over to Group II at the time of disease progression.
Group II (varlilumab, nivolumab)
EXPERIMENTALPatients receive varlilumab IV over 90 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also receive nivolumab IV over 30 minutes every 2 weeks for 4 months and every 4 weeks for a total of up to 2 years in the absence of disease progression or unacceptable toxicity.
Interventions
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- Patients must have a histopathologically confirmed diagnosis of an aggressive B-cell non-Hodgkin lymphoma that is recurrent or refractory to standard therapy
- For the purpose of this study, aggressive B-cell NHL will be deemed any lymphoma belonging to one of the following groups according to the 2016 revision of the World Health Organization (WHO) classification of lymphoid neoplasms
- For the purposes of stratification, diagnoses are grouped into 2 categories:
- Category A
- Burkitt lymphoma
- Burkitt-like lymphoma with 11q aberration
- High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements
- High-grade B-cell lymphoma, not otherwise specified (NOS)
- Category B
- Diffuse large B-cell lymphoma (DLBCL), NOS
- Diffuse large B-cell lymphoma (DLBCL), NOS; germinal center B-cell type
- Diffuse large B-cell lymphoma (DLBCL), NOS; activated B-cell type
- Large B-cell lymphoma with IRF4 rearrangement
- T-cell/histiocyte-rich large B-cell lymphoma
- Primary DLBCL of the central nervous system (CNS)
- +25 more criteria
You may not qualify if:
- Patient has received chemotherapy, targeted agent, or radiotherapy within 4 weeks or at least 5 half-lives, whichever is longer, prior to registration
- Palliative (limited-field) radiation therapy is permitted, if all of the following criteria are met:
- Repeat imaging demonstrates no new sites of bone metastases
- The lesion being considered for palliative radiation is not a target lesion
- Patient has received immunotherapy (including monoclonal antibodies) within 4 weeks prior to registration
- Patients who have not recovered to grade 1 or less from any adverse events due to agents administered more than 4 weeks earlier (excluding alopecia)
- Patients who are receiving any other investigational agents
- Patients should be excluded if they have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
- Patients who have received autologous stem cell transplant (ASCT) =\< 12 weeks prior to the first dose of study drug
- Patients with a prior history of allogeneic stem cell or solid organ transplantation
- Patients with evidence of active disease in the central nervous system (CNS) defined as either the presence of active lesions on MRI obtained within 4 weeks of registration or progressive neurological decline
- Patients with primary CNS lymphoma who develop systemic recurrence following standard therapy may be included as long as no active CNS disease is present at the time or enrollment; similarly, patients with secondary involvement of the CNS from a systemic lymphoma may be included as long as the CNS disease has been optimally treated and they demonstrate no evidence of active CNS disease
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to CDX-1127 (varlilumab) and/or nivolumab
- History of severe hypersensitivity reaction to any monoclonal antibody
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- +14 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (33)
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, 85054, United States
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259, United States
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980, United States
Moffitt Cancer Center-International Plaza
Tampa, Florida, 33607, United States
Moffitt Cancer Center - McKinley Campus
Tampa, Florida, 33612, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Northside Hospital
Atlanta, Georgia, 30342, United States
Northwestern University
Chicago, Illinois, 60611, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
University of Kansas Clinical Research Center
Fairway, Kansas, 66205, United States
HaysMed
Hays, Kansas, 67601, United States
University of Kansas Cancer Center
Kansas City, Kansas, 66160, United States
Lawrence Memorial Hospital
Lawrence, Kansas, 66044, United States
The University of Kansas Cancer Center - Olathe
Olathe, Kansas, 66061, United States
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, 66210, United States
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas, 66211, United States
Mercy Hospital Pittsburg
Pittsburg, Kansas, 66762, United States
Salina Regional Health Center
Salina, Kansas, 67401, United States
University of Kansas Health System Saint Francis Campus
Topeka, Kansas, 66606, United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141, United States
University Health Truman Medical Center
Kansas City, Missouri, 64108, United States
University of Kansas Cancer Center - North
Kansas City, Missouri, 64154, United States
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, 64064, United States
University of Kansas Cancer Center at North Kansas City Hospital
North Kansas City, Missouri, 64116, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Siteman Cancer Center-South County
St Louis, Missouri, 63129, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Stephen Ansell
- Organization
- Mayo Clinic
Study Officials
- PRINCIPAL INVESTIGATOR
Stephen M Ansell
Dana-Farber - Harvard Cancer Center LAO
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 31, 2017
First Posted
February 1, 2017
Study Start
December 21, 2018
Primary Completion
May 26, 2023
Study Completion (Estimated)
October 24, 2026
Last Updated
November 10, 2025
Results First Posted
October 16, 2024
Record last verified: 2025-10