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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
44
Pembrolizumab 400 mg IV
Doxorubicin 25mg/m2 IV
Vinblastine 6mg/m2 IV
Dacarbazine 375mg/m2 IV
Brentuximab vedotin 1.8 mg/kg IV
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
RECRUITINGUniversity of Pennsylvania
Philadelphia, Pennsylvania, United States
NOT_YET_RECRUITINGUniversity of Virginia
Charlottesville, Virginia, United States
RECRUITINGComplete Remission Rate
Evaluate complete remission rate as defined by LYRIC criteria at end of induction in fit and unfit older participants with cHL following anthracycline-based chemotherapy.
Time frame: 2 years
Incidence of grade 3-5 treatment-related AEs
Assess tolerance and safety of a fitness-adapted pembrolizumab-based regimen in fit older participants with cHL based on incidence of grade 3-5 treatment-related AEs (CTCAE v5.0)
Time frame: 2 years
2-year PFS, 2-year OS, 2-year Lymphoma Specific Survival in the fit older population following pembrolizumab-based adaptive therapy
Evaluate the efficacy, as determined by the 2-year progression free survival (PFS), overall survival (OS), and 2-year lymphoma specific survival in the fit older population.
Time frame: 2 years
Complete remission rate (by LYRIC criteria), 2-year PFS, 2-year OS, 2-year Lymphoma Specific Survival in the Frail older population
Evaluate the efficacy of a chemotherapy-free approach (pembrolizumab plus BV), as determined by the complete remission rate (LYRIC criteria), 2-year progression free survival (PFS), overall survival (OS), and 2-year lymphoma specific survival in participants who are not frail for anthracycline-based therapy.
Time frame: 2 years
Complete remission rate (LYRIC criteria) after lead-in BV/pembrolizumab
Assess the efficacy of short course lead-in therapy and correlation with end-induction treatment efficacy for all participants.
Time frame: 2 years
Incidence of grade 2-5 immune-related toxicities (CTCAE v5.0)
Assess safety, as determined by the frequency of higher-grade immune-related adverse events for all participants.
Time frame: 2 years
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