Fitness-adapted, Pembrolizumab-based Therapy for Untreated Classical Hodgkin Lymphoma Patients 60 Years of Age and Above (cHL 001)
This is a multi-center, open-label phase II study to assess the efficacy of a novel fitness-adapted regimen in previously untreated older patients with classical Hodgkin lymphoma. All participants will receive up to a total of 8 cycles of pembrolizumab (Q6 week dosing). The first cycle of pembrolizumab will be administered in combination with brentuximab vedotin (BV) (lead-in treatment). Following lead-in treatment, all participants will undergo interim PET/CT (iPET) as well as fitness testing to help inform participant level of fitness for subsequent lymphoma-directed therapies. Participants deemed Frail by this assessment will continue 3 additional 6 week cycles of concurrent pembrolizumab and BV (induction therapy, each cycle is 42 days), then continue single-agent pembrolizumab to complete up to 4 additional cycles (i.e., 8 total) of therapy (consolidation and maintenance therapy, Frail cohort). Two additional BV doses will be given as consolidation, at days 1 and 22 of pembrolizumab cycle 5. Those deemed fit after lead-in therapy (Fit cohort) will continue pembrolizumab and switch from BV to concurrently-administered combination chemotherapy using doxorubicin (A), vinblastine (V), and dacarbazine (D) for a total of 4 planned AVD cycles (3, 6-week pembrolizumab cycles, induction therapy). Chemotherapy drugs will be given at standard doses as in ABVD (no bleomycin will be given in this study) on days 1 and 15 of each 28-day cycle (C1AVD), and pembrolizumab dosing will remain every 42 days. Following end-induction PET/CT, pembrolizumab will continue every 42 days for up to 4 cycles in the consolidation/maintenance phase. Two additional BV doses will be given as consolidation, at days 1 and 22 of pembrolizumab cycle 5. Participants deemed unfit after lead-in therapy and by fitness assessment will continue pembrolizumab and switch from BV to concurrently administered combination chemotherapy termed mini-avd as induction therapy. Mini-avd consists of lower doses of conventional AVD chemotherapy (doxorubicin, vinblastine and dacarbazine) and will be administered for on days 1 and 15 of a 28 day cycle for 4 planned cycles. Pembrolizumab will continue every 42 days. Following end-induction PET/CT, pembrolizumab will continue every 42 days for up to 4 cycles in the consolidation/maintenance phase. Two additional BV doses will be given as consolidation, at days 1 and 22 of pembrolizumab cycle 5.
• Participants of any sex who are ≥60 years of age on day 1, cycle 1.
• The participant must be willing and able to provide written informed consent for the trial and participate in all planned study procedures.
• Histologically confirmed diagnosis of classical Hodgkin lymphoma
• PET-avid, measurable disease (≥1.5cm bi-dimensional measurement)
• Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to
• PS 2 may be allowed at the discretion of the treating investigator if impairment is considered to be primarily lymphoma-related. Evaluation of ECOG is to be performed within 10 days prior to the date of registration.
• Participants who have received involved field radiation will be allowed. However, they will be excluded if any of the following are true:
‣ Radiation was dosed ≤6 months from registration.
⁃ Radiation was delivered to \> 1 lymph node group as defined by the NCCN criteria.
⁃ The radiation dose was ≥30 Gy.
⁃ The participant has radiation-related toxicities ≥ Grade 2 at the time of registration.
⁃ The participant requires corticosteroids for radiation-related toxicities at the time of registration (regardless of dose).
⁃ The participant has ever experienced radiation pneumonitis.
• Have adequate organ function as defined per protocol. Specimens must be collected within 10 days prior to registration (confirmation of eligibility).