ctDNA-Guided Therapy for Relapsed/Refractory Hodgkin Lymphoma
brief summary
This is a single arm, open-label, multicenter, phase II study of pembrolizumab (pembro), gemcitabine, vinorelbine, and liposomal doxorubicin (GVD) in patients with relapsed or refractory classic Hodgkin lymphoma (cHL) with response-adapted consolidation. This study will investigate using circulating tumor DNA (ctDNA) at pre-determined time points using Foresight CLARITY LDT, an ultra-sensitive liquid biopsy platform that detects Minimal residual disease (MRD) in patients with B-cell lymphomas using the phased variant enrichment and sequencing technology (PhasEDq) to determine response to study interventions.
detailed description
PRIMARY OBJECTIVE:
I. To determine the ctDNA/MRD-negative, PET-negative complete response rate for cHL patients undergoing treatment with pembro + GVD.
SECONDARY OBJECTIVES:
I. To determine progression-free survival (PFS) overall survival (OS) at 2 years among patients receiving non-transplant consolidation.
II. To determine PFS and OS at 2 years for the overall cohort.
III. To determine the proportion of patients treated with pembro + GVD and non-transplant consolidation who ultimately undergo Autologous Stem Cell Transplant (ASCT) within 2 years.
IV. To determine the rate of discordance between Positron Emission Tomography (PET)/Computerized tomography (CT) response and ctDNA/MRD response.
V. To determine the incidence of adverse events, including immune-related adverse events, in patients receiving pembro + GVD and pembrolizumab consolidation.
VI. To assess health-related quality of life (HRQOL) and patient-reported outcomes (PROs) as measured by Patient-Reported Outcomes Measurement Information System (PROMIS) 29 and Functional Assessment of Cancer Therapy-COmprehensive Score for financial Toxicity (FACIT-COST).
VII. To determine the proportion of patients with relapsed or refractory cHL for whom baseline Foresight CLARITY LDT genotyping from the peripheral blood is successful
EXPLORATORY OBJECTIVES:
I. To evaluate the kinetics of ctDNA/MRD clearance in the peripheral blood after pembro + GVD.
II. To evaluate the ctDNA/MRD-negative complete response (CR) rate and 2-year PFS stratified by cHL molecular subgroup at diagnosis (H1 vs H2 genotype).
III. To evaluate long term efficacy and toxicity outcomes for up to 5 years.
IV. To compare the performance of identification of phased variants from plasma genotyping with identification of phased variants from archival tissue genotyping.
official title
Pembrolizumab and GVD With ctDNA-guided Consolidation in Patients With Relapsed or Refractory Classic Hodgkin Lymphoma: A Multicenter Phase 2 Study of the University of California Hematologic Malignancies Consortium