ctDNA-Guided Therapy for Relapsed/Refractory Hodgkin Lymphoma

NCT07021989 | Not Yet Recruiting Phase 2 DMC FDA Drug FDA Device

• 2 other identifiers: 25255NCI-2025-04294
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 6

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.

Conditions

Hodgkin Lymphoma, Adult; Refractory Hodgkin Lymphoma; Classic Hodgkin Lymphoma

Keywords

circulating tumor DNA

Outcome Measures

Primary Outcomes (1)

• Percentage of participants with a complete response

  To determine the ctDNA/MRD negative, PET negative complete response rate for cHL, participants undergoing treatment with pembro + GVD will have a composite response incorporating the following two criteria: (1) Absence of detectable cHL ctDNA as assessed by Foresight CLARITY LDT after 2 cycles of treatment and (2) complete response by Fluorodeoxyglucose (FDG) PET/CT, assessed by Lugano criteria after 2 cycles, or 4 if participant demonstrates indeterminate response (IR) after 2 cycles. Lugano classification for response using FDG PET-CT is as follows: A score is given which ranges from 1 (No uptake above background) to 5 (Hottest area of uptake markedly \> liver and/or new lesions present). A CR is defined as a score of 1,2,3 in nodal or extranodal sites with or without a residual mass. Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) will be used to distinguish IR, SD or PD. Response rate will be summarized by percentage, along with 95% confidence intervals.

  Up to 4 cycles (a cycle is 21 days)

Secondary Outcomes (11)

• Progression-free survival (PFS) rate for participants without Autologous Stem Cell Transplant (ASCT)

  Up to 2 years

• Overall Survival (OS) rate for participants without ASCT

  Up to 2 years

• Overall PFS rate

  Up to 2 years

• Overall survival rate

  Up to 2 years

• Proportion of participants undergoing ASCT

  Up to 2 years

Study Arms (1)

Treatment (Pembrolizumab + GVD)

EXPERIMENTAL

All participants receive 2, 21-day cycles of 200 mg Pembrolizumab (pembro) on day 1 of each cycle (pembro) and 1000mg Gemcitabine, 20mg/m\^2 of Vinorelbine, Liposomal doxorubicin 15 mg/m2 (GVD) on days 1 and 8 of each cycle for up to 2 cycles. Pegfilgrastim is administered on day 8 or 9 of each cycle. FDG-PET/CT imaging and Foresight CLARITY LDT ctDNA response after 2 cycles will determine if participants are eligible for an additional 2 cycles of pembro + GVD or salvage therapy and ASCT. Participants may be able to qualify for consolidation without ASCT (pembro and/or 30 Gy ISRT) depending on response. Radiographic response after 4 cycles will be conducted to determine eligibility for consolidation without ASCT for participants with CR or standard of care salvage therapy and ASCT, for participants with partial response (PR), stable disease (SD), or progressive disease (PD) after a second administration of pembro+GVD. Participants are followed for up to 5 years.

Drug: Pembrolizumab; Radiation: Non-investigational, involved site radiotherapy (ISRT); Drug: Gemcitabine; Drug: Vinorelbine; Drug: Liposomal Doxorubicin; Device: Foresight CLARITY™ LDT; Drug: Pegfilgrastim; Procedure: Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)/Computerized tomography (CT)

Interventions

Pembrolizumab DRUG

Given intravenously

Also known as: Keytruda

Treatment (Pembrolizumab + GVD)

Non-investigational, involved site radiotherapy (ISRT) RADIATION

Undergo possible, standard of care, non-investigational radiation therapy

Also known as: ISRT

Treatment (Pembrolizumab + GVD)

Gemcitabine DRUG

Given IV

Also known as: Gemzar

Treatment (Pembrolizumab + GVD)

Vinorelbine DRUG

Given IV

Also known as: Navelbine

Treatment (Pembrolizumab + GVD)

Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)/Computerized tomography (CT) PROCEDURE

Undergo imaging

Also known as: FDG PET/CT

Treatment (Pembrolizumab + GVD)

Liposomal Doxorubicin DRUG

Given IV

Also known as: Doxil

Treatment (Pembrolizumab + GVD)

Foresight CLARITY™ LDT DEVICE

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

Also known as: CLARITY LDT™

Treatment (Pembrolizumab + GVD)

Pegfilgrastim DRUG

Given IV for supportive care

Also known as: Neulasta

Treatment (Pembrolizumab + GVD)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Histologically confirmed classic Hodgkin lymphoma (including nodular sclerosis, lymphocyte-rich, mixed cellularity, and lymphocyte-depleted Hodgkin lymphoma).
• Participants must have relapsed or refractory disease after no more than one line of systemic therapy. First line therapy must have included doxorubicin.
• At least one site of FDG-avid disease on PET/CT that is ≥ 1.5 cm in diameter for nodal disease or ≥ 1.0 cm in diameter if extranodal disease.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (Karnofsky ≥ 50%).
• Demonstrates adequate organ function as defined below:
• Absolute neutrophil count (ANC) ≥ 1.0 X 10\^9/ L (1000/microliter (mcL), growth factors permitted).
• Platelets ≥ 75 X 10\^9 / L (75,000/mcL, platelet transfusion independent).
• Total bilirubin ≤ 1.5 x institutional upper limit of normal, unless elevated due to Gilbert's syndrome.
• Aspartate aminotransferase (AST) / (SGOT) ≤3 x institutional upper limit of normal.
• Alanine aminotransferase (ALT) / (SGPT) ≤3 x institutional upper limit of normal.
• Creatinine clearance (CrCl, calculated) ≥ 40 mL/min/1.73 m\^2, calculated using the Cockcroft-Gault equation.
• For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• Individuals with a history of hepatitis C virus (HCV) infection must have been treated with sustained virologic response. For individuals with HCV infection who are currently on treatment, participants are eligible if there is an undetectable HCV viral load.
• Human immunodeficiency virus (HIV)-infected individuals on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.

You may not qualify if:

• Participants who previously received a programmed cell death protein 1 (PD-1) inhibitor-based regimen (e.g., nivolumab or pembrolizumab + AVD) and progressed within 6 months of last done of immune checkpoint inhibitor.
• Receipt of systemic anti-cancer therapies or radiation within 2 weeks prior to the start of trial therapy or receipt of antibody therapy within 4 weeks prior to the start of trial therapy.
• Has participated in a study of an investigational product and received study treatment or used an investigational device within four weeks of the first dose of treatment.
• Prior autologous or allogeneic hematopoietic stem cell transplant.
• Systemic autoimmune disease requiring continuous immunosuppressive treatment (≥prednisone 10 mg per day or equivalent), with the exception of autoimmune thyroid disease.
• Left ventricular ejection fraction (LVEF) \<50% as assessed by transthoracic echocardiogram or multigated acquisition (MUGA) scan.
• Participants whose lifetime cumulative dose of doxorubicin would exceed 450 mg/m\^2 after receiving 4 cycles of pembro + GVD are excluded (i.e., \>330 mg/m\^2 at trial entry).
• Has known hypersensitivity to pembrolizumab, gemcitabine, vinorelbine, and/or liposomal doxorubicin; or any of their excipients.
• Has any significant medical condition or comorbidity that could compromise participants safety in the opinion of the treating investigator (e.g., uncontrolled serious infection).
• Individuals with ongoing Grade 2 events that are not clinically stable or ongoing ≥ Grade 3 events (CTCAE v5.0 grading).
• Notification from Foresight Diagnostics that the CLARITY LDT baseline specimen has failed sample quality control (QC) and/or the baseline ctDNA is not quantifiable. Note: Foresight will only notify sites if the specimen fails quality control (QC) or is not quantifiable. Sites will not receive notification if the specimen passes QC and is quantifiable. For QC failures, a sample re-draw may be considered upon discussion with and approval by the lead University of California, San Francisco (UCSF) Principal Investigator.
• Individuals with any condition or social circumstance that, in the opinion of the investigator, would impair the participant's ability to comply with study activities, interfere with participant safety, or study endpoints.

Sponsors & Collaborators

• Michael Spinner, MD: lead
• UC Hematologic Malignancies Consortium (UCHMC): collaborator
• Gateway for Cancer Research: collaborator
• Foresight Diagnostics, Inc.: collaborator
• Natera, Inc.: collaborator

Study Sites (6)

University of California Davis

Davis, California, 95616, United States

Location

University of California San Francisco-Fresno

Fresno, California, 93701, United States

Location

University of California Irvine

Irvine, California, 92617, United States

Location

University of California, San Diego

La Jolla, California, 92093, United States

Location

Unversity of California, Los Angeles

Los Angeles, California, 90095, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Related Publications (1)

• Ma S, Spinner MA. Optimizing the Role of Checkpoint Inhibitors in the Management of Hodgkin Lymphoma. J Natl Compr Canc Netw. 2026 Feb;24(2):e257125. doi: 10.6004/jnccn.2025.7125.

  PMID: 41698326 DERIVED

MeSH Terms

Conditions

Hodgkin Disease

Interventions

pembrolizumab; Gemcitabine; Vinorelbine; liposomal doxorubicin; pegfilgrastim; Fluorodeoxyglucose F18; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Deoxyglucose; Deoxy Sugars; Carbohydrates; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Michael Spinner, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

UCSF Hematopoietic Malignancies Clinical Trial Recruitment

CONTACT

877-827-3222; HDFCCC.Heme@ucsf.edu

Nickole Criner

CONTACT

877-827-3222; cancertrials@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: June 6, 2025
• First Posted: June 15, 2025
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): May 31, 2029
• Study Completion (Estimated): December 31, 2033
• Last Updated: June 4, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: During the course of study activities

Locations

US (6)