Nivolumab With or Without Varlilumab in Treating Patients With Relapsed or Refractory Aggressive B-cell Lymphomas

Running, not enrolling · Phase 2

Conditions studied: ALK-Positive Large B-Cell Lymphoma, Diffuse Large B-Cell Lymphoma Activated B-Cell Type, Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation, Diffuse Large B-Cell Lymphoma Germinal Center B-Cell Type, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, EBV-Positive Mucocutaneous Ulcer, HHV8-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements, High Grade B-Cell Lymphoma, Not Otherwise Specified, Intravascular Large B-Cell Lymphoma, Large B-Cell Lymphoma With 11q Aberration, Large B-Cell Lymphoma With IRF4 Rearrangement, Plasmablastic Lymphoma, Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System, Primary Effusion Lymphoma, Recurrent B-Cell Non-Hodgkin Lymphoma, Recurrent Burkitt Lymphoma, Recurrent Diffuse Large B-Cell Lymphoma, Recurrent Gray-Zone Lymphoma, Recurrent High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, Recurrent High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements, Recurrent Lymphomatoid Granulomatosis, Recurrent Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type, Recurrent Primary Mediastinal Large B-Cell Lymphoma, Recurrent T-Cell/Histiocyte-Rich Large B-Cell Lymphoma, Refractory B-Cell Non-Hodgkin Lymphoma, Refractory Burkitt Lymphoma, Refractory Diffuse Large B-Cell Lymphoma, Refractory Gray-Zone Lymphoma, Refractory High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, Refractory High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements, Refractory Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type, Refractory Primary Mediastinal Large B-Cell Lymphoma, Refractory T-Cell/Histiocyte-Rich Large B-Cell Lymphoma

In brief

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.

Key facts

Study ID: NCT03038672
Run by: National Cancer Institute (NCI)
People needed: 54
Starts: 2018-12-21
Expected to finish: 2026-10-24
Last updated by the study team: 2026-05-12

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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)
Primary cutaneous DLBCL, leg type
Epstein-Barr virus (EBV)+ DLBCL, NOS
EBV+ mucocutaneous ulcer
DLBCL associated with chronic inflammation
Lymphomatoid granulomatosis
Primary mediastinal (thymic) large B-cell lymphoma
Intravascular large B-cell lymphoma
ALK+ large B-cell lymphoma
Plasmablastic lymphoma
Primary effusion lymphoma

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
Pregnant women are excluded from this study because CDX-1127 (varlilumab) and nivolumab are agents with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CDX-1127 (varlilumab) or nivolumab, breastfeeding should be discontinued if the mother is treated with CDX-1127 (varlilumab) or nivolumab
Patients with human immunodeficiency virus (HIV) are eligible for the study provided they meet the other protocol criteria in addition to the following:
Undetectable HIV load by standard polymerase chain reaction (PCR) clinical assay within 60 days prior to registration
Absolute CD4 count of >= 200 mm\^3 within 60 days prior to registration
Willing to maintain adherence to combination antiretroviral therapy
No history of acquired immunodeficiency syndrome (AIDS) defining condition (other than lymphoma or CD4 cell count < 200 mm\^3)
Likely to have near normal lifespan if not for the presence of relapsed/refractory lymphoma
Patients with evidence of hepatitis B virus (HBV) are eligible provided there is minimal hepatic injury and the patient has undetectable HBV on suppressive HBV therapy; patient must be willing to maintain adherence to HBV therapy
Patients with previously treated and eradicated hepatitis C virus (HCV) who have minimal hepatic injury are eligible
Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, should be excluded; these include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease; patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible; patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible

Where it is running

Mayo Clinic Hospital in Arizona — Phoenix, Arizona, United States
Mayo Clinic in Arizona — Scottsdale, Arizona, United States
Mayo Clinic in Florida — Jacksonville, Florida, United States
Moffitt Cancer Center-International Plaza — Tampa, Florida, United States
Moffitt Cancer Center - McKinley Campus — Tampa, Florida, United States
Moffitt Cancer Center — Tampa, Florida, United States
Northside Hospital — Atlanta, Georgia, United States
Northwestern University — Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center — Chicago, Illinois, United States
University of Kansas Clinical Research Center — Fairway, Kansas, United States
HaysMed — Hays, Kansas, United States
University of Kansas Cancer Center — Kansas City, Kansas, United States
Lawrence Memorial Hospital — Lawrence, Kansas, United States
The University of Kansas Cancer Center - Olathe — Olathe, Kansas, United States
University of Kansas Cancer Center-Overland Park — Overland Park, Kansas, United States
University of Kansas Hospital-Indian Creek Campus — Overland Park, Kansas, United States
Mercy Hospital Pittsburg — Pittsburg, Kansas, United States
Salina Regional Health Center — Salina, Kansas, United States
University of Kansas Health System Saint Francis Campus — Topeka, Kansas, United States
University of Kansas Hospital-Westwood Cancer Center — Westwood, Kansas, United States
Mayo Clinic in Rochester — Rochester, Minnesota, United States
Siteman Cancer Center at Saint Peters Hospital — City of Saint Peters, Missouri, United States
Siteman Cancer Center at West County Hospital — Creve Coeur, Missouri, United States
University Health Truman Medical Center — Kansas City, Missouri, United States
University of Kansas Cancer Center - North — Kansas City, Missouri, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.