Pembrolizumab Followed by Chemotherapy for the Treatment of Patients With Classical Hodgkin Lymphoma

PRIMARY OBJECTIVE: I. To assess the percent of patients that achieve a complete response (CR) after frontline pembrolizumab monotherapy induction, among classic Hodgkin lymphoma (cHL) patients with early unfavorable or advanced stage disease, per Lugano 2014 response criteria at positron emission tomography (PET) #2. SECONDARY OBJECTIVES: I. To assess the efficacy of a reduced number of cycles (2-4) of doxorubicin (adriamycin), vinblastine, and dacarbazine (AVD) when used following treatment with frontline pembrolizumab monotherapy in classic Hodgkin lymphoma (cHL), per Lugano 2014 Response Criteria. II. To assess the safety and tolerability of sequential immunotherapy with upfront pembrolizumab followed by AVD chemotherapy in cHL per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (ver.) 5.0. III. To assess progression-free-survival (PFS) of cHL patients who received sequential immunotherapy with upfront pembrolizumab followed by AVD chemotherapy, assessed by central review, according to Lugano 2014 Response Criteria. IV. To assess overall survival (OS) of cHL patients who received sequential immunotherapy with upfront pembrolizumab followed by AVD chemotherapy. V. To assess the CR rate at the end of pembrolizumab (PEM) induction by PET-computed tomography (CT) in all treated patients, regardless of number of cycles of PEM received, per Lugano 2014 Response Criteria. OUTLINE: INDUCTION: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 of each cycle. Treatment repeats repeat every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo disease assessment. Patients with a response complete 3 additional cycles of pembrolizumab, undergo disease assessment and proceed to consolidation. Patients without response or with progressive disease proceed to consolidation. CONSOLIDATION: Patients receive doxorubicin IV, vinblastine IV and dacarbazine IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity for 2 to 6 cycles dependent upon response and disease type. Patients undergo echocardiography/ multigated acquisition (MUGA) scan, CT scan, PET scan and blood sample collection throughout the study and may undergo tumor biopsy during screening. After completion of study treatment, patients are followed up at 30 days, every 3 months for 1 year, and every 6 months for 4 years.