Hodgkin Lymphoma, AdultPhase 2NCT07021989
ctDNA-Guided Therapy for Relapsed/Refractory Hodgkin Lymphoma
A Phase 2 study testing Pembrolizumab, Non-investigational, involved site radiotherapy (ISRT) and Gemcitabine in people with Hodgkin Lymphoma, Adult and Refractory Hodgkin Lymphoma, run by Michael Spinner, MD at 6 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hodgkin Lymphoma, Adult, Refractory Hodgkin Lymphoma, Classic Hodgkin Lymphoma
- What is being tested?
- Pembrolizumab, Non-investigational, involved site radiotherapy (ISRT) and Gemcitabine
- Type of treatment
- Injection or infusion, Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 6 sitesUnited States
- Study dates
- 18 Aug 2026to 31 Mar 2034
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
- Individuals with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
- Females of reproductive potential (defined below) must be willing to undergo a urine or serum pregnancy test (i.e., human chorionic gonadotropin test) within 72 hours before start of trial therapy. A female is considered to not be of reproductive potential (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice), if the participants meet either of the following two criteria: (1) has reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause); or (2) has undergone surgical sterilization (i.e., hysterectomy and/or bilateral oophorectomy for removal of uterus and/or ovaries). The result of the urine or serum pregnancy test must be negative in order to administer initiate trial therapy. If a urine pregnancy test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the individual must be excluded from participation if the serum pregnancy result is positive. Pregnant individuals are excluded from this study because there is a potential risk for adverse effects in the unborn child secondary to treatment of the study participant with trial therapy.
- Ability to understand and willingness to sign a written informed consent document.
Who cannot join
- 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.
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- 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 who are pregnant or breast-feeding/chest-feeding. Pregnant and breastfeeding individuals are excluded because there is a potential risk for adverse effects in the unborn/nursing child secondary to treatment of the study participant with trial therapies. Females of reproductive potential must have a negative pregnancy test before initiation of trial therapy, as outlined in inclusion criterion #12. Breast-feeding should be discontinued before initiation of trial therapy.
- 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.
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
6 sites in 1 country
United States6 sites, 6 recruiting
- Not yet recruiting
University of California Davis
Davis, California, 95616
- Not yet recruiting
University of California San Francisco-Fresno
Fresno, California, 93701
- Not yet recruiting
University of California Irvine
Irvine, California, 92617
- Not yet recruiting
University of California, San Diego
La Jolla, California, 92093
- Not yet recruiting
Unversity of California, Los Angeles
Los Angeles, California, 90095
- Recruiting
University of California, San Francisco
San Francisco, California, 94143
UCSF Hematopoietic Malignancies Clinical Trial Recruitment, 877-827-3222, HDFCCC.Heme@ucsf.edu
Nickole Criner, cancertrials@ucsf.edu
About this study
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
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.
Read the detailed description
PRIMARY OBJECTIVE:
- To determine the ctDNA/MRD-negative, PET-negative complete response rate for cHL patients undergoing treatment with pembro + GVD.
SECONDARY OBJECTIVES:
- 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.
- 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:
- 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.
- Being tested
- Pembrolizumab, Non-investigational, involved site radiotherapy (ISRT), Gemcitabine, Vinorelbine, Liposomal Doxorubicin
- Keywords
- circulating tumor DNA
- Medical subject headings
- Hodgkin Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called Keytruda
Given intravenously
Non-investigational, involved site radiotherapy (ISRT)Radiation
Also called ISRT
Undergo possible, standard of care, non-investigational radiation therapy
GemcitabineDrug
Also called Gemzar
Given IV
VinorelbineDrug
Also called Navelbine
Given IV
Liposomal DoxorubicinDrug
Also called Doxil
Given IV
Foresight CLARITY™ LDTDevice
Also called 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
PegfilgrastimDrug
Also called Neulasta
Given IV for supportive care
Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)/Computerized tomography (CT)Procedure or surgery
Also called FDG PET/CT
Undergo imaging
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
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.
Measured: Up to 2 years
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.
Measured: Up to 2 years
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.
Measured: Up to 2 years
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.
Measured: Up to 2 years
Proportion of participants undergoing ASCT
The proportion of participants undergoing ASCT is defined as the number of participants having received an autologous stem cell graft over the total number of participants.
Measured: Up to 2 years
Percentage of participants with presence cHL ctDNA
The percentage of participants with the presence of absence of detectable ctDNA through 2 cycles of pembrolizumab (pembro) + GVD will be reported.
Measured: Up to
Percentage of participants with presence of detectable metabolically active disease
The percentage of participants with the presence of absence of detectable metabolically active disease on an FDG PET/CT at any time during the course of treatment with Pembro+GVD will be reported.
Measured: Up to 2 years
Number of participants reporting treatment-emergent Adverse Events (AEs) of significant interest
The number of participants reporting Adverse Events (AEs) will be descriptive and performed based on the safety population. Serious Adverse Events (SAEs), Immune-related Adverse Events (irAEs), AEs classified as Grade 3 or higher per NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5, and AEs resulting in discontinuation of treatment, withdrawal from the study will be tabulated.
Measured: From start of treatment until 90 days after discontinuation of treatment, approximately 2 years
Change in mean scores on the Patient Reported Outcomes Measurement Information System (PROMIS®-29) (Version 2) over time
The PROMIS 29 v2.0 profile assesses pain intensity using a response scale for each item ranging from 0 (no pain) to 10 (worst imaginable pain) on seven health domains (physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance), with four items per domain and one question which addresses pain intensity item. PROMIS-29 domains are scored using a T-score metric, with higher scores indicate higher levels of functioning. Mean scores and standard deviations will be reported.
Measured: Up to 5 years
Change in mean scores on the Comprehensive Score for Financial Toxicity-Functional Assessment of Chronic Illness Therapy (COST-FACIT) survey over time
The COST-FACIT is an 11-item measure used to assess financial toxicity. Each item is measured on a five-point Likert scale (0 = not at all, 4 = very much), with recall based on the past 7 days related to the participant's disease management. A score is computed by first reverse coding seven items, then taking the sum of all items, multiplying the sum by the number of items on the scale, and dividing that number by the number of items answered. Higher scores indicate better Financial Well-Being. Mean scores and standard deviations will be reported.
Measured: Up to 5 years
Percentage of participants with detectable cHL ctDNA at baseline
Percentage of all participants with detectable cHL ctDNA in the plasma at baseline will be reported. Participants not meeting this criterion will be excluded from the study, but genotype failures will be recorded for the purpose of this endpoint.
Measured: Up to 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2025
- Study start18 Aug 2026
- Primary completion31 Jul 2029 (estimated)
- Study completion31 Mar 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hodgkin Lymphoma, AdultStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 38 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Michael Spinner, MD
- Sponsor type
- University, hospital or other
- Collaborators
- UC Hematologic Malignancies Consortium (UCHMC), Foresight Diagnostics, Inc., Natera, Inc., Gateway for Cancer Research
- Responsible party
- Sponsor-investigator, Michael Spinner, MD, University of California, San Francisco
- Investigators
- Michael Spinner, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07021989
- Sponsor's protocol ID
- 25255
- Other IDs
- NCI-2025-04294
- Status last verified
- Oct 2026
- First submitted
- 6 Jun 2025
- Last updated
- 20 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: De-identified data will be shared with participating research collaborators during the course of the study.
Publications
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.
PubMed 41698326
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT07021989
- Acronym / sponsor ID
- 25255
- Keywords
- circulating tumor DNA
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 38 participants (estimated)
- Lead sponsor
- Michael Spinner, MDUniversity, hospital or other
- Collaborators
- UC Hematologic Malignancies Consortium (UCHMC), Foresight Diagnostics, Inc., Natera, Inc., Gateway for Cancer Research
- Study start
- 18 Aug 2026 (actual)
- Primary completion
- 31 Jul 2029 (estimated)
- Study completion
- 31 Mar 2034 (estimated)
- First posted
- 15 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- To determine the ctDNA/MRD-negative, PET-negative complete response rate for cHL patients undergoing treatment with pembro + GVD.
SECONDARY OBJECTIVES:
- 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.
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (Pembrolizumab + GVD) | Experimental | 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)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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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%).
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabAlso: KeytrudaGiven intravenously | Drug | Treatment (Pembrolizumab + GVD) |
| Non-investigational, involved site radiotherapy (ISRT)Also: ISRTUndergo possible, standard of care, non-investigational radiation therapy | Radiation | Treatment (Pembrolizumab + GVD) |
| GemcitabineAlso: GemzarGiven IV | Drug | Treatment (Pembrolizumab + GVD) |
| VinorelbineAlso: NavelbineGiven IV | Drug | Treatment (Pembrolizumab + GVD) |
| Liposomal DoxorubicinAlso: DoxilGiven IV | Drug | Treatment (Pembrolizumab + GVD) |
| Foresight CLARITY™ LDTAlso: 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 | Device | Treatment (Pembrolizumab + GVD) |
| PegfilgrastimAlso: NeulastaGiven IV for supportive care | Drug | Treatment (Pembrolizumab + GVD) |
| Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)/Computerized tomography (CT)Also: FDG PET/CTUndergo imaging | Procedure or surgery | Treatment (Pembrolizumab + GVD) |
Primary outcome
Percentage of participants with a complete response
Time frame: Up to 4 cycles (a cycle is 21 days)
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.
11 secondary outcomes
Progression-free survival (PFS) rate for participants without Autologous Stem Cell Transplant (ASCT)
Time frame: Up to 2 years
Overall Survival (OS) rate for participants without ASCT
Time frame: Up to 2 years
Overall PFS rate
Time frame: Up to 2 years
Overall survival rate
Time frame: Up to 2 years
Proportion of participants undergoing ASCT
Time frame: Up to 2 years
Percentage of participants with presence cHL ctDNA
Time frame: Up to
Percentage of participants with presence of detectable metabolically active disease
Time frame: Up to 2 years
Number of participants reporting treatment-emergent Adverse Events (AEs) of significant interest
Time frame: From start of treatment until 90 days after discontinuation of treatment, approximately 2 years
Change in mean scores on the Patient Reported Outcomes Measurement Information System (PROMIS®-29) (Version 2) over time
Time frame: Up to 5 years
Change in mean scores on the Comprehensive Score for Financial Toxicity-Functional Assessment of Chronic Illness Therapy (COST-FACIT) survey over time
Time frame: Up to 5 years
Percentage of participants with detectable cHL ctDNA at baseline
Time frame: Up to 30 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2026.
- Derived from this study: PubMed 41698326Ma 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.
- Individual participant dataSharing planned: Yes. De-identified data will be shared with participating research collaborators during the course of the study.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Michael Spinner, MD principal investigator
University of California, San Francisco
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab, Non-investigational, involved site radiotherapy (ISRT) and Gemcitabine in people with Hodgkin Lymphoma, Adult and Refractory Hodgkin Lymphoma, run by Michael Spinner, MD at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact UCSF Hematopoietic Malignancies Clinical Trial Recruitment (877-827-3222, HDFCCC.Heme@ucsf.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of participants with a complete response (time frame: Up to 4 cycles (a cycle is 21 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07021989, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2026.