Pembrolizumab in Combination With Chemotherapy for the Treatment of Frail Hodgkin Lymphoma Patients Ineligible for Standard Treatment

NCT07275216 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 24081NCI-2025-08524P30CA033572
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial tests how well pembrolizumab in addition to chemotherapy (gemcitabine, brentuximab vedotin, and dacarbazine) works in treating frail patients with newly diagnosed Hodgkin lymphoma who aren't candidates for standard anthracycline-based treatment. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Gemcitabine is a chemotherapy drug that blocks the cells from making deoxyribonucleic acid (DNA) and may kill cancer cells. Brentuximab vedotin is in a class of medications called antibody-drug conjugates. It is made of a monoclonal antibody called brentuximab that is linked to a cytotoxic agent called vedotin. Brentuximab attaches to CD30 positive lymphoma cells in a targeted way and delivers vedotin to kill them. Dacarbazine is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill cancer cells and slow down or stop cancer growth. Pembrolizumab in combination chemotherapy may be a safe and effective alternative treatment option for frail patients with Hodgkin lymphoma who can't receive standard anthracycline-based treatment.

Conditions

Classic Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Complete metabolic response (CMR) to pembrolizumab and gemcitabine (P-G)

  Will be estimated by the proportion of response-evaluable patients achieving a best response of CMR, along with the 95% exact binomial confidence interval.

  During/after cycles 1-8 of P-G (cycle length = 21 days), before initiation of salvage or maintenance therapy or non-protocol lymphoma therapy

Secondary Outcomes (12)

• CMR

  During/after cycles 1-8 of P-G (cycle length = 21 days) or cycles 1-4 of pembrolizumab maintenance (cycle length = 42 days), before initiation of non-protocol lymphoma therapy

• Overall response (OR)

  During/after cycles 1-8 of P-G (cycle length = 21 days) or cycles 1-4 of pembrolizumab maintenance (cycle length = 42 days), before initiation of non-protocol lymphoma therapy

• Progression-free survival (PFS)

  From start of P-G treatment to time of disease relapse/progression or death, assessed up to 24 months

• Duration of response (DOR)

  From first achievement of CMR or PMR during/after cycles 1-8 of P-G (cycle length = 21 days) or cycles 1-4 of pembrolizumab maintenance (cycle length = 42 days) to disease relapse/progression or death, assessed up to 24 months

• Overall survival (OS)

  From start of P-G treatment to time of death, assessed up to 24 months

Study Arms (1)

Treatment (P-G, P-BV-D)

EXPERIMENTAL

See Detailed Description.

Procedure: Biospecimen Collection; Drug: Brentuximab Vedotin; Procedure: Computed Tomography; Drug: Dacarbazine; Procedure: Echocardiography Test; Drug: Gemcitabine; Biological: Pembrolizumab; Other: Physical Performance Testing; Procedure: Positron Emission Tomography; Procedure: Pulmonary Function Test

Interventions

Brentuximab Vedotin DRUG

Given IV

Also known as: ADC SGN-35, Adcetris, Anti-CD30 Antibody-Drug Conjugate SGN-35, Anti-CD30 Monoclonal Antibody-MMAE SGN-35, Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35, cAC10-vcMMAE, SGN 35, SGN-35, SGN35

Treatment (P-G, P-BV-D)

Computed Tomography PROCEDURE

Undergo PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (P-G, P-BV-D)

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Treatment (P-G, P-BV-D)

Gemcitabine DRUG

Given IV

Also known as: dFdC, dFdCyd, Difluorodeoxycytidine

Treatment (P-G, P-BV-D)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: BCD-201, GME 751, GME751, Keytruda, Lambrolizumab, MK 3475, MK-3475, MK3475, Pembrolizumab Biosimilar BCD-201, Pembrolizumab Biosimilar GME751, Pembrolizumab Biosimilar QL2107, Pembrolizumab Biosimilar RPH-075, Pembrolizumab Biosimilar SB27, QL2107, RPH 075, RPH-075, RPH075, SB 27, SB-27, SB27, SCH 900475, SCH-900475, SCH900475

Treatment (P-G, P-BV-D)

Physical Performance Testing OTHER

Ancillary studies

Also known as: Physical Fitness Testing, Physical Function Testing

Treatment (P-G, P-BV-D)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Treatment (P-G, P-BV-D)

Pulmonary Function Test PROCEDURE

Ancillary studies

Also known as: lung function test, PFT, Pulmonary Function Testing, Pulmonary Function Tests

Treatment (P-G, P-BV-D)

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (P-G, P-BV-D)

Dacarbazine DRUG

Given IV

Also known as: 4-(Dimethyltriazeno)imidazole-5-carboxamide, 5-(Dimethyltriazeno)imidazole-4-carboxamide, Asercit, Biocarbazine, Dacarbazina, Dacarbazina Almirall, Dacarbazine - DTIC, Dacatic, Dakarbazin, Deticene, Detimedac, DIC, Dimethyl (triazeno) imidazolecarboxamide, Dimethyl Triazeno Imidazol Carboxamide, Dimethyl Triazeno Imidazole Carboxamide, dimethyl-triazeno-imidazole carboxamide, Dimethyl-triazeno-imidazole-carboximide, DTIC, DTIC-Dome, Fauldetic, Imidazole Carboxamide, Imidazole Carboxamide Dimethyltriazeno, WR-139007

Treatment (P-G, P-BV-D)

Eligibility Criteria

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

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Assent, when appropriate, will be obtained per institutional guidelines
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies
• If unavailable, exceptions may be granted with study principal investigator (PI) approval
• Meets at least one of the following criteria indicating unsuitability for conventional anthracycline-based frontline chemotherapy, as determined by the investigator:
• Age ≥ 75 years
• Eastern Cooperative Oncology Group (ECOG) 2-4
• Left ventricular ejection fraction (LVEF) \< 50%
• Creatinine clearance \< 60 mL/min, using Cockcroft-Gault formula or equivalent
• Pulmonary function impairment: forced expiratory volume in 1 second (FEV1) \< 50% and/or diffusion capacity of the lung for carbon monoxide (DLCO) \< 50%
• ECOG ≤ 2
• Age ≥ 18 years
• Histologically confirmed new diagnosis of classical Hodgkin lymphoma (excluding nodular lymphocyte predominant Hodgkin lymphoma) according to the World Health Organization (WHO) classification, with hematopathology review at the participating institution
• No prior systemic treatment for classical Hodgkin lymphoma with the following exceptions: a course of systemic corticosteroids for palliation of symptoms related to the classical Hodgkin lymphoma is allowed but must be stopped by cycle 1 day 1 (C1D1) as well as prior treatment with P-G as part of this clinical trial for patients will receive P-BV-D
• Measurable disease (at least one non-bone fludeoxyglucose F-18 \[FDG\]-avid lesion ≥ 1.5 cm in long axis)

You may not qualify if:

• Concomitant investigational therapy
• Live vaccine within 30 days prior to day 1 of protocol therapy (e.g. measles, mumps, rubella, varicella, yellow fever, rabies, Bacille Calmette Guerin \[BCG\], oral polio vaccine, and oral typhoid)
• Grade ≥ 2 peripheral neuropathy
• Requirement for hemodialysis or peritoneal dialysis. Estimated glomerular filtration rate (EGFR) \> 30 for pembrolizumab + BV + dacarbazine
• Known active central nervous system (CNS) involvement by lymphoma including parenchymal and/or lymphomatous meningitis
• History of prior ≥ grade 3 hypersensitivity to either brentuximab vedotin or pembrolizumab
• Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment)
• History of another primary malignancy that has been in remission for fewer than 3 years, with the following exceptions:
• Non-melanoma skin cancer treated with curative intent
• In situ cervical cancer
• If the malignancy is expected to not require any systemic treatment for at least 2 years (this exception should be discussed with the study PI)
• Condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration. Exceptions are:
• Inhaled or topical steroids and
• Adrenal replacement doses \> 10 mg daily prednisone equivalents in the absence of active autoimmune disease
• Up to 7 days of 20 mg daily prednisone equivalent after C1D1 for management of lymphoma-related symptoms

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• City of Hope Medical Center: lead

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Interventions

Specimen Handling; Brentuximab Vedotin; Dacarbazine; Gemcitabine; pembrolizumab; Exercise Test; Magnetic Resonance Spectroscopy; Respiratory Physiological Phenomena

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Respiratory Function Tests; Diagnostic Techniques, Respiratory System; Ergometry; Spectrum Analysis; Chemistry Techniques, Analytical; Circulatory and Respiratory Physiological Phenomena

Study Officials

• Matthew Mei

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 28, 2025
• First Posted: December 10, 2025
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): October 20, 2029
• Study Completion (Estimated): October 20, 2029
• Last Updated: April 23, 2026

Record last verified: 2026-04

Locations

US (1)