This phase II trial studies how well brentuximab vedotin and nivolumab work in treating patients with stage I-II classic Hodgkin lymphoma. Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30 positive cancer cells in a targeted way and delivers vedotin to kill them. 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.
PRIMARY OBJECTIVE: I. Determine the 18-month progression free survival (PFS) for each arm of therapy stratified by positron emission tomography (PET)/computed tomography (CT)-2 response. SECONDARY OBJECTIVES: I. Assess safety, tolerability, and quality of life (QOL) for each arm of therapy. II. Measure PET/CT-2 negativity rate after 2 lead-in cycles of standard of care doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD). III. Evaluate the 3-year PFS and overall survival (OS) for each arm of treatment. EXPLORATORY OBJECTIVES: I. Evaluate if a baseline antitumor immune response, as assessed by a Nanostring gene panel, correlates with PFS. II. Evaluate if minimal residual disease (MRD) status, as monitored by cancer personalized profiling by deep sequencing (CAPP-Seq) of circulating tumor (ct) deoxyribonucleic acid (DNA), can be correlated with PFS. OUTLINE: Patients are assigned to 1 of 2 groups based on their PET/CT-2 scans. GROUP I (PET/CT-2 NEGATIVE): Patients without bulky disease are randomized to either Arm A or B and patients with bulky disease are assigned to Arm B. ARM A: Patients receive brentuximab vedotin intravenously (IV) over 30 minutes and nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive doxorubicin IV, bleomycin IV, vinblastine IV, dacarbazine IV on days 1 and 15. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 60 minutes on day 1. Treatment with nivolumab repeats every 14 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. GROUP II (PET/CT-2 POSITIVE): Patients receive doxorubicin IV, vinblastine IV, dacarbazine, IV and brentuximab vedotin IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients that are PET/CT negative receive nivolumab IV over 60 minutes on day 1. Treatment with nivolumab repeats every 14 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months for 3 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
155
Given IV
Given IV
Given IV
Given IV
Given IV
Ancillary studies
Given IV
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
City of Hope Medical Center
Duarte, California, United States
University of California San Diego
San Diego, California, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States
Northwestern University
Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Massachusetts General Hospital
Charlestown, Massachusetts, United States
Hackensack University Medical Center
Hackensack, New Jersey, United States
...and 7 more locations
18-month Progression-free survival (PFS) for each arm of therapy
Will be estimated using the method of Kaplan and Meier.
Time frame: Up to 18 months
Incidence of adverse events evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0
Frequency tables will be used to summarize toxicity profile.
Time frame: Up to 3 years
Scores from European Organisation for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire C30, version 3 (EORTC-C30) for each arm of therapy
All of the scales range in score from 0 to 100. A high score for a functional scale represents a high/healthy level of functioning whereas a high score for a symptom scale or item represents a high level of symptomatology or problems.
Time frame: Up to 3 years
Positron emission tomography/computed tomography-2 negativity rate
Will be estimated using the Deauville 5-point score/2014 Lugano Classsification
Time frame: After 2 courses of ABVD (each course is 28 days)
3-year PFS for each arm of treatment
Will be estimated using the method of Kaplan and Meier.
Time frame: Up to 3 years
Overall survival for each arm of treatment
Will be estimated using the method of Kaplan and Meier.
Time frame: Up to 3 years
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