This phase II trial studies how well nivolumab and brentuximab vedotin work in treating older patients with untreated Hodgkin lymphoma. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Biological therapies, such as brentuximab vedotin, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Nivolumab and brentuximab vedotin may work better in treating older patients with untreated Hodgkin lymphoma.
PRIMARY OBJECTIVE: I. To determine the efficacy based on overall metabolic response rate (partial metabolic response \[PMR\] + complete metabolic remission \[CMR\]) of brentuximab vedotin/nivolumab in previously untreated Hodgkin lymphoma patients 60 years of age or older, or those considered unsuitable for standard chemotherapy because of a low cardiac ejection fraction (\< 50%) or impaired pulmonary or renal function. SECONDARY OBJECTIVES: I. The complete metabolic response (CMR) rate. II. Safety and tolerability of the regimen in this patient population. III. Duration of response (DOR). IV. Progression-free survival (PFS). V. Overall survival (OS). CORRELATIVE RESEARCH OBJECTIVES: I. T-cell/cytokine - peripheral blood specimens will be used to assess T-cell activation and cytokine up regulation as measures of treatment effect. II. Biomarkers - intratumoral cell populations, genetic variability, serum cytokines and T-cell activation will be evaluated to identify potential biomarkers that correlate with response to therapy. OUTLINE: Patients receive brentuximab vedotin intravenously (IV) over 30 minutes and nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for 7 cycles and 6-8 weeks in cycle 8 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 30 days for 90 days, every 90 days for 2.5 years, and then every 6 months until 5 years from registration.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
46
Given IV
Given IV
Stanford Cancer Institute Palo Alto
Palo Alto, California, United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States
Mayo Clinic
Rochester, Minnesota, United States
Washington University School of Medicine
St Louis, Missouri, United States
Hackensack University Medical Center
Hackensack, New Jersey, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
M D Anderson Cancer Center
Houston, Texas, United States
Overall Metabolic Response Rate
The primary endpoint of this trial is the rate (percentage) of overall metabolic response. A metabolic response is defined as a participant who has achieved an objective status of Partial metabolic response (PMR) or Complete metabolic response (CMR) at the end of cycle 8. Response is based on PET/CT based on the revised 2014 Lugano Classification. (PMR: Score 4 (uptake moderately \> liver) or 5 (uptake markedly higher than liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size CMR: Score 1 (no uptake above background), 2 (uptake\<=mediastinum), or 3 (uptake \> mediastinum but \<= liver) with or without a residual mass on PET Deauville 5-Point-Scale. The scale ranges from 1 to 5, where 1 is best and 5 is the worst.
Time frame: Up to 8 cycles of treatment (approximately 29 weeks)
Number of Participants With an Overall Response of Complete Metabolic Response
The number of participants with an overall response of Complete metabolic response. Response is based on PET/CT based on the revised 2014 Lugano Classification. (CMR: Score 1 (no uptake above background), 2 (uptake\<=mediastinum), or 3 (uptake \> mediastinum but \<= liver) with or without a residual mass on PET Deauville 5-Point-Scale. The scale ranges from 1 to 5, where 1 is best and 5 is the worst.
Time frame: Up to end of course 8
Duration of Response (DOR)
DOR is time from the date at which the patient's objective status is first noted to be a CMR or PMR to the earliest date progression (progressive metabolic disease \[PMD\] or progressive disease \[PD\]) is documented. Response is based on PET/CT based on the revised 2014 Lugano Classification. (PMR: Score 4 (uptake moderately \> liver) or 5 (uptake markedly higher than liver and/or new lesions) CMR: Score 1 (no uptake above background), 2 (uptake\<=mediastinum), or 3 (uptake \> mediastinum but \<= liver) with or without a residual mass on PET Deauville 5-Point-Scale. The scale ranges from 1 to 5, where 1 is best and 5 is the worst. PMD: Score 4 or 5 with an increase in intensity of uptake from baseline and/or New FDG-avid foci consistent with lymphoma at interim or end-of-treatment assessment PD: An individual node/lesion must be abnormal with: LDi \> 1.5 cm and Increase by ≥ 50% from PPD nadir and, An increase in LDi or SDi from nadir, 0.5 cm for lesions ≤2 cm, 1.0 cm for lesions \> 2 cm)
Time frame: 30 months
Progression-free Survival
Progression-free survival is defined as the time from registration to the earliest date of documentation of disease progression (Progressive metabolic disease (PMD) or Progressive disease (PD)) or death due to any cause. Response is based on PET/CT based on the revised 2014 Lugano Classification. (PMD: Score 4 or 5 with an increase in intensity of uptake from baseline and/or New FDG-avid foci consistent with lymphoma at interim or end-of-treatment assessment PD: An individual node/lesion must be abnormal with: LDi \> 1.5 cm and Increase by ≥ 50% from PPD nadir and, An increase in LDi or SDi from nadir, 0.5 cm for lesions ≤2 cm, 1.0 cm for lesions \> 2 cm)
Time frame: 30 months
Overall Survival
The distribution of overall survival will be estimated using the method of Kaplan-Meier.
Time frame: 30 months
Number of Participants Experiencing at Least One Adverse Events Graded 3 or Higher Deemed at Least Possibly Related to Treatment
Number of participants experiencing at least one toxicity. Toxicity is defined as an adverse event graded 3 or higher by Common Terminology Criteria for Adverse Events version 4.0 deemed at least possibly related to treatment.
Time frame: Up to 8 cycles of treatment (approximately 29 weeks)
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