Pembrolizumab in Combination With Chemotherapy for the Treatment of Frail Hodgkin Lymphoma Patients Ineligible for Standard Treatment

Inclusion Criteria

• •Documented informed consent of the participant and/or legally authorized representative
• •* Assent, when appropriate, will be obtained per institutional guidelines
• •Agreement to allow the use of archival tissue from diagnostic tumor biopsies
• •* If unavailable, exceptions may be granted with study principal investigator (PI) approval
• •Meets at least one of the following criteria indicating unsuitability for conventional anthracycline-based frontline chemotherapy, as determined by the investigator:
• •* Age ≥ 75 years
• •* Eastern Cooperative Oncology Group (ECOG) 2-4
• •* Left ventricular ejection fraction (LVEF) \< 50%
• •* Creatinine clearance \< 60 mL/min, using Cockcroft-Gault formula or equivalent
• •* Pulmonary function impairment: forced expiratory volume in 1 second (FEV1) \< 50% and/or diffusion capacity of the lung for carbon monoxide (DLCO) \< 50%
• •ECOG ≤ 2
• •Age ≥ 18 years
• •Histologically confirmed new diagnosis of classical Hodgkin lymphoma (excluding nodular lymphocyte predominant Hodgkin lymphoma) according to the World Health Organization (WHO) classification, with hematopathology review at the participating institution
• •No prior systemic treatment for classical Hodgkin lymphoma with the following exceptions: a course of systemic corticosteroids for palliation of symptoms related to the classical Hodgkin lymphoma is allowed but must be stopped by cycle 1 day 1 (C1D1) as well as prior treatment with P-G as part of this clinical trial for patients will receive P-BV-D
• •Measurable disease (at least one non-bone fludeoxyglucose F-18 \[FDG\]-avid lesion ≥ 1.5 cm in long axis)
• •Absolute neutrophil count (ANC) ≥ 1,000/mm\^3
• •* NOTE: Growth factor is not permitted within 7 days of ANC assessment unless cytopenia is secondary to disease involvement
• •Platelets ≥ 50,000/mm\^3
• •* NOTE: Platelet transfusions are not permitted within 7 days of platelet assessment unless cytopenia is secondary to disease involvement
• •Total bilirubin ≤ 2 × upper limit of normal (ULN) or direct bilirubin ≤ 2 × ULN for patients with Gilbert's disease
• •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN
• •AST and ALT ≤ 3 x ULN unless there is liver involvement by lymphoma in which case AST and ALT \< 5 x ULN
• •For patients for whom P-BV-D therapy is planned, creatinine clearance of ≥ 30 mL/min per 24-hour urine test or the Cockcroft-Gault formula
• •If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin (PT) ≤ 1.5 x ULN
• •* If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants
• •If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN
• •* If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants
• •Seronegative for hepatitis C virus (HCV), hepatitis B virus (HBV) (surface antigen negative) OR
• •* If seropositive for HBV or HCV, nucleic acid quantitation must be performed. Viral load must be undetectable. Patients with occult or prior HBV infection (defined as negative hepatitis B virus surface antigen \[HBsAg\] and positive hepatitis B core antibody \[HBcAb\]) may be included if HBV DNA is undetectable, if they are willing to undergo DNA testing on day 1 of every cycle and every three months for at least 12 months after the last cycle of study treatment
• •Women of childbearing potential (WOCBP): negative urine or serum pregnancy test
• •* If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• •A male participant must agree to use a contraception during the treatment period and for at least 6 months after the last dose of study treatment and refrain from donating sperm during this period
• •A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• •* Not a woman of childbearing potential (WOCBP) OR
• •* A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least (X days/weeks \[corresponding to time needed to eliminate any study treatment(s)\] \[pembrolizumab and/or any active comparator/combination\] plus 30 days \[a menstruation cycle\] for study treatments with risk of genotoxicity) after the last dose of study treatment
• •TO PROCEED WITH SALVAGE TREATMENT: ECOG ≤ 2
• •TO PROCEED WITH SALVAGE TREATMENT: Resolution of treatment-related adverse events (AEs) to baseline or grade 1, whichever is higher
• •TO PROCEED WITH SALVAGE TREATMENT: Measurable disease (at least one non-bony FDG-avid lesion ≥ 1.5 cm in long axis)
• •TO PROCEED WITH SALVAGE TREATMENT: Peripheral neuropathy ≤ grade 2
• •TO PROCEED WITH SALVAGE TREATMENT: ANC ≥ 1,000/mm\^3
• •* NOTE: Growth factors are permitted
• •TO PROCEED WITH SALVAGE TREATMENT: Platelets ≥ 50,000/mm\^3
• •* NOTE: Platelet transfusions are permitted
• •TO PROCEED WITH SALVAGE TREATMENT: Hemoglobin ≥ 8 g/dL (no transfusion allowed within 3 days prior to screening)
• •TO PROCEED WITH SALVAGE TREATMENT: Total bilirubin ≤ 2 x ULN or direct bilirubin ≤ 2 x ULN for patients with Gilbert's disease
• •TO PROCEED WITH SALVAGE TREATMENT: AST ≤ 3 x ULN, or less then 5 x ULN for patients with liver involvement by lymphoma
• •TO PROCEED WITH SALVAGE TREATMENT: ALT ≤ 3 x ULN, or less then 5 x ULN for patients with liver involvement by lymphoma
• •TO PROCEED WITH SALVAGE TREATMENT: Creatinine clearance of ≥ 30 mL/min per 24-hour urine test or the Cockcroft-Gault formula
• •HIV positive
• •History of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association class III-IV within 6 months prior to day 1 of protocol therapy
• •Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
• •Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)