NCT07021989

ctDNA-Guided Therapy for Relapsed/Refractory Hodgkin Lymphoma

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

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 38 (estimated)
• Sponsor: Michael Spinner, MD · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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. OUTLINE: Participants will undergo response assessment and ctDNA/MRD assessment using phased variant enrichment and detection sequencing (PhasED-Seq) using Foresight CLARITY LDT. A composite response assessment will be used to determine eligibility for non-transplant consolidation. Participants who achieve a response after 2 cycles of pembro + GVD will be eligible for non-transplant consolidation with 8 cycles of pembrolizumab and/or 30 Gray (Gy) involved-site radiotherapy (ISRT). Participants not achieving a response will discontinue study therapy and proceed to study follow-up, during which time participants can receive standard of care salvage therapy and ASCT, if eligible. Participants will be followed for up to 5 years from trial entry for long term efficacy and toxicity outcomes.

Conditions

• Hodgkin Lymphoma, Adult
• Refractory Hodgkin Lymphoma
• Classic Hodgkin Lymphoma

Interventions

Type	Name	Description
DRUG	Pembrolizumab	Given intravenously
RADIATION	Non-investigational, involved site radiotherapy (ISRT)	Undergo possible, standard of care, non-investigational radiation therapy
DRUG	Gemcitabine	Given IV
DRUG	Vinorelbine	Given IV
DRUG	Liposomal Doxorubicin	Given IV
DEVICE	Foresight CLARITY™ LDT	Foresight CLARITY LDT, a laboratory-developed test (LDT),by Foresight Diagnostics, is an ultra-sensitive liquid biopsy and tissue platform that detects MRD in patients with B-cell lymphomas
DRUG	Pegfilgrastim	Given IV for supportive care
PROCEDURE	Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)/Computerized tomography (CT)	Undergo imaging

Timeline

• Start date: 2026-05-01
• Primary completion: 2029-03-31
• Completion: 2033-10-31
• First posted: 2025-06-15
• Last updated: 2026-03-17

Locations

6 sites across 1 country: United States

Regulatory

• FDA-regulated drug study
• FDA-regulated device study