Pembrolizumab Before and After Autologous Stem Cell Transplant for the Treatment of Relapsed or Refractory Classical Hodgkin Lymphoma

Inclusion Criteria

• SCREENING: Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of relapsed or refractory Hodgkin’s lymphoma will be enrolled in this study
• SCREENING: Eligible for autologous stem cell transplant (ASCT) with BEAM conditioning regimen
• SCREENING: Karnofsky performance status (KPS) greater than 70 or Eastern Cooperative Oncology Group (ECOG) ≤ 1
• SCREENING: Absolute neutrophil count (ANC) ≥ 1500/µL (within 14 days of study registration)
• SCREENING: Platelets ≥ 100,000/µL (50,000/µL if known bone marrow involvement) (within 14 days of study registration)
• SCREENING: Creatinine clearance by Cockroft-Gault of ≥ 40 mL/minute (within 14 days of study registration)
• SCREENING: Total bilirubin off < 1.5 times upper limit of institutional normal (within 14 days of study registration)
• SCREENING: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 times upper limit of institutional normal (within 14 days of study registration)
• SCREENING: International normalized ratio (INR) and partial thromboplastin time (PTT) < 1.5 upper limit of institutional normal (within 14 days of study registration)
• SCREENING: Women of childbearing potential and men with partners of child-bearing potential must agree to use of contraception for the duration of treatment and 4 months (120 days) after the last dose of study drug
• SCREENING: Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) anti viral therapy for at least 4 weeks, and have undetectable HBV viral load prior to randomization * Note: Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention
• SCREENING: Participants with a history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening * Note: Participants must have completed curative anti-viral therapy at least 4 weeks prior to randomization
• SCREENING: HIV-infected participants must have well-controlled HIV on antiretroviral therapy (ART), defined as: * Participants on ART must have a CD4+ T-cell count ≥ 350 cells/mm^3 at the time of screening * Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV ribonucleic acid (RNA) level below 50 or the lower limit of quantitation (LLOQ) (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks before screening * It is advised that participants must not have had any AIDS defining opportunistic infections within the past 12 months * Participants on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks before study entry (day 1) and agree to continue ART throughout the study
• SCREENING: Able to provide written voluntary consent prior to the performance of any research related tests or procedures
• DAY -6 PRE ASCT/ADMISSION: Eligible for autologous stem cell transplant (ASCT) with BEAM conditioning regimen
• DAY -6 PRE ASCT/ADMISSION: KPS greater than 70 or ECOG ≤ 1
• DAY -6 PRE ASCT/ADMISSION: Absolute neutrophil count (ANC) ≥ 1500/µL (within 14 days of day -6)
• DAY -6 PRE ASCT/ADMISSION: Platelets ≥ 100,000/µL (50,000/µL if known bone marrow involvement) (within 14 days of day -6)
• DAY -6 PRE ASCT/ADMISSION: Creatinine clearance by Cockroft-Gault of ≥ 40 mL/minute (within 14 days of day -6)
• DAY -6 PRE ASCT/ADMISSION: Total bilirubin of < 1.5 times upper limit of institutional normal (within 14 days of day -6)
• DAY -6 PRE ASCT/ADMISSION: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 times upper limit of institutional normal (within 14 days of day -6)
• DAY -6 PRE ASCT/ADMISSION: INR and PTT < 1.5 upper limit of institutional normal (within 14 days of day -6)
• DAY -6 PRE ASCT/ADMISSION: Women of childbearing potential and men with partners of child-bearing potential must agree to use of contraception for the duration of treatment and 4 months (120 days) after the last dose of study drug
• DAY +30 POST ASCT/PEMBROLIZUMAB MAINTENANCE: KPS greater than 70 or ECOG ≤ 1
• DAY +30 POST ASCT/PEMBROLIZUMAB MAINTENANCE: Absolute neutrophil count (ANC) ≥ 1000/µL (within 14 days of day +30/dose 1 of maintenance)
• DAY +30 POST ASCT/PEMBROLIZUMAB MAINTENANCE: Platelets ≥ 75,000/µL (within 14 days of day +30/dose 1 of maintenance)
• DAY +30 POST ASCT/PEMBROLIZUMAB MAINTENANCE: Creatinine clearance by Cockroft-Gault of ≥ 40 mL/minute (within 14 days of day +30/dose 1 of maintenance)
• DAY +30 POST ASCT/PEMBROLIZUMAB MAINTENANCE: Total bilirubin of < 1.5 times upper limit of institutional normal (within 14 days of day +30/dose 1 of maintenance)
• DAY +30 POST ASCT/PEMBROLIZUMAB MAINTENANCE: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 times upper limit of institutional normal (within 14 days of day +30/dose 1 of maintenance)
• DAY +30 POST ASCT/PEMBROLIZUMAB MAINTENANCE: INR and PTT < 1.5 upper limit of institutional normal (within 14 days of day +30/dose 1 of maintenance)
• DAY +30 POST ASCT/PEMBROLIZUMAB MAINTENANCE: Women of childbearing potential and men with partners of child-bearing potential must agree to use of contraception for the duration of treatment and 4 months (120 days) after the last dose of study drug

Exclusion Criteria

• Patients with prior history of any grade 2 or higher autoimmune reaction to PD-1 inhibitors, necessitating permanent discontinuation of the PD-1 inhibitor or necessitating systemic immunosuppressants
• Patients who are refractory to PD-1 inhibitor therapy, defined as having progressive disease while on PD-1 based therapy
• Has received prior radiotherapy within 2 weeks of start of study intervention or radiation-related toxicities requiring corticosteroids * Note: Two weeks or fewer of palliative radiotherapy for non-central nervous system (CNS) disease is permitted. The last radiotherapy treatment must have been performed at least 7 days before the first dose of study intervention
• Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed * Any licensed coronavirus disease-2019 (COVID-19) vaccine (including for emergency use) in a particular country is allowed in the study as long as they are messenger ribonucleic acid (mRNA) vaccines, replication-incompetent adenoviral vaccines, or inactivated vaccines
• Has received any chemotherapy within 3 weeks prior to the first dose of study intervention
• Has received any immuno-oncology therapy other than pembrolizumab, any investigational agents, or has used an investigational device within 3 half-lives prior to study intervention administration * Participants may receive pembrolizumab, but not within 3 weeks prior to initial study intervention as per standard dosing for Hodgkin lymphoma
• Known additional malignancy that is progressing or has required active treatment within the past 2 years * Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded * Participants with low-risk early-stage prostate cancer (T1-T2a, Gleason score ≤ 6, and prostate-specific antigen (PSA) < 10 ng/mL) either treated with definitive intent or untreated in active surveillance with stable disease are not excluded
• Has known active CNS disease * Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention
• History of or active autoimmune disease, or other syndrome that requires systemic steroids or autoimmune agents * Exceptions: Participants with vitiligo, resolved childhood asthma or atopy, hypothyroidism, or Sjogren's syndrome, as well as participants requiring only intranasal steroids, intermittent use of bronchodilators, local steroid injections, or physiologic replacement doses of prednisone ( ≤ 10 mg/d) may enroll
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Has an active infection requiring systemic therapy
• Hepatitis B with detectable titer (defined as HBsAg reactive) or known active hepatitis C virus (defined as detectable HCV RNA [qualitative]) infection (history of previous adequately treated infection that is undetectable at time of enrollment is not an exclusion)
• Has not adequately recovered from major surgery or has ongoing surgical complications
• Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant’s participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• HIV-infected participants with a history of Kaposi’s sarcoma and/or multicentric Castleman’s disease
• Has had an allogenic tissue/solid organ transplant
• Pregnant or breastfeeding as agents used in this study are pregnancy category D (positive evidence of risk). Females of childbearing potential must have a negative pregnancy test (serum or urine) within 14 days of study registration
• Ineligibility to proceed to ASCT at principal investigator (PI) or treating physician’s judgement