ctDNA-Guided Therapy for Relapsed/Refractory Hodgkin Lymphoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorMichael Spinner, MD
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Single group
Treatments tested in this trial
Pembrolizumab
DrugGiven intravenously
Non-investigational, involved site radiotherapy (ISRT)
RadiationUndergo possible, standard of care, non-investigational radiation therapy
Gemcitabine
DrugGiven IV
Vinorelbine
DrugGiven IV
Liposomal Doxorubicin
DrugGiven IV
Foresight CLARITY™ LDT
DeviceForesight 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
Pegfilgrastim
DrugGiven IV for supportive care
Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)/Computerized tomography (CT)
Procedure/SurgeryUndergo imaging
Treatment groups
38 Participants
are divided into 1 treatment groupGroup A: Treatment (Pembrolizumab + GVD)Experimental treatment 8 interventions
Trial outcomes
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.
Time frame
Up to 4 cycles (a cycle is 21 days)Secondary outcomes
1
Progression-free survival (PFS) rate for participants without Autologous Stem Cell Transplant (ASCT)
PFS rate is defined as the proportion of participants alive without disease from initiation of study therapy to progression or death by any cause, whichever occurs first for up to 2 years after participants receive study therapy and non-transplant consolidation. The censoring time for PFS will be the date of the last study assessment for progression. PFS will be analyzed descriptively using Kaplan-Meier methods.
Time frame
Up to 2 years2
Overall Survival (OS) rate for participants without ASCT
OS rate is defined as the proportion of participants alive from initiation of study therapy to death by any cause for up to 2 years after participants receive study therapy and non-transplant consolidation. The censoring time for OS will be the date of the last study contact. OS will be analyzed descriptively using Kaplan-Meier methods.
Time frame
Up to 2 years3
Overall PFS rate
Overall PFS rate is defined as proportion of participants alive without disease from initiation of study therapy to progression or death by any cause, whichever occurs first for up to 2 years after participants receive study therapy. The censoring time for PFS will be the date of the last study assessment for progression. PFS will be analyzed descriptively using Kaplan-Meier methods.
Time frame
Up to 2 years4
Overall survival rate
OS rate is defined as the proportion of participants alive from initiation of study therapy to death by any cause for up to 2 years after participants receive study therapy. The censoring time for OS will be the date of the last study contact. OS will be analyzed descriptively using Kaplan-Meier methods.
Time frame
Up to 2 yearsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Michael Spinner, MD
Lead sponsor
University of California, San Francisco
Sponsor institution
UC Hematologic Malignancies Consortium (UCHMC)
Collaborator
Foresight Diagnostics, Inc.
Collaborator
Natera, Inc.
Collaborator
Gateway for Cancer Research
Collaborator
Source ClinicalTrials.gov