Recruiting

Phase 2

Pembrolizumab & Gemcitabine, Brentuximab Vedotin, DacarbazinePembrolizumab in Combination With Chemotherapy for the Treatment of Frail Hodgkin Lymphoma Patients Ineligible for Standard Treatment

Sponsor:

City of Hope Medical Center

Code:

NCT07275216

Conditions

Classic Hodgkin Lymphoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Brentuximab Vedotin

Computed Tomography

Dacarbazine

Echocardiography Test

Study Details

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

Study ID

NCT07275216

Start date

Oct 1, 2026

Status verified date

Aug, 2026

Completion date

Oct 20, 2029

Anticipated

Primary completion date

Oct 20, 2029

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

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)
Absolute neutrophil count (ANC) ≥ 1,000/mm\^3

NOTE: Growth factor is not permitted within 7 days of ANC assessment unless cytopenia is secondary to disease involvement
Platelets ≥ 50,000/mm\^3

NOTE: Platelet transfusions are not permitted within 7 days of platelet assessment unless cytopenia is secondary to disease involvement
Total bilirubin ≤ 2 × upper limit of normal (ULN) or direct bilirubin ≤ 2 × ULN for patients with Gilbert's disease
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN
AST and ALT ≤ 3 x ULN unless there is liver involvement by lymphoma in which case AST and ALT < 5 x ULN
For patients for whom P-BV-D therapy is planned, creatinine clearance of ≥ 30 mL/min per 24-hour urine test or the Cockcroft-Gault formula
If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin (PT) ≤ 1.5 x ULN

If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants
If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN

If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants
Seronegative for hepatitis C virus (HCV), hepatitis B virus (HBV) (surface antigen negative) OR

If seropositive for HBV or HCV, nucleic acid quantitation must be performed. Viral load must be undetectable. Patients with occult or prior HBV infection (defined as negative hepatitis B virus surface antigen \[HBsAg\] and positive hepatitis B core antibody \[HBcAb\]) may be included if HBV DNA is undetectable, if they are willing to undergo DNA testing on day 1 of every cycle and every three months for at least 12 months after the last cycle of study treatment
Women of childbearing potential (WOCBP): negative urine or serum pregnancy test

If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
A male participant must agree to use a contraception during the treatment period and for at least 6 months after the last dose of study treatment and refrain from donating sperm during this period
A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:

Not a woman of childbearing potential (WOCBP) OR
A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least (X days/weeks \[corresponding to time needed to eliminate any study treatment(s)\] \[pembrolizumab and/or any active comparator/combination\] plus 30 days \[a menstruation cycle\] for study treatments with risk of genotoxicity) after the last dose of study treatment
TO PROCEED WITH SALVAGE TREATMENT: ECOG ≤ 2
TO PROCEED WITH SALVAGE TREATMENT: Resolution of treatment-related adverse events (AEs) to baseline or grade 1, whichever is higher
TO PROCEED WITH SALVAGE TREATMENT: Measurable disease (at least one non-bony FDG-avid lesion ≥ 1.5 cm in long axis)
TO PROCEED WITH SALVAGE TREATMENT: Peripheral neuropathy ≤ grade 2
TO PROCEED WITH SALVAGE TREATMENT: ANC ≥ 1,000/mm\^3

NOTE: Growth factors are permitted
TO PROCEED WITH SALVAGE TREATMENT: Platelets ≥ 50,000/mm\^3

NOTE: Platelet transfusions are permitted
TO PROCEED WITH SALVAGE TREATMENT: Hemoglobin ≥ 8 g/dL (no transfusion allowed within 3 days prior to screening)
TO PROCEED WITH SALVAGE TREATMENT: Total bilirubin ≤ 2 x ULN or direct bilirubin ≤ 2 x ULN for patients with Gilbert's disease
TO PROCEED WITH SALVAGE TREATMENT: AST ≤ 3 x ULN, or less then 5 x ULN for patients with liver involvement by lymphoma
TO PROCEED WITH SALVAGE TREATMENT: ALT ≤ 3 x ULN, or less then 5 x ULN for patients with liver involvement by lymphoma
TO PROCEED WITH SALVAGE TREATMENT: Creatinine clearance of ≥ 30 mL/min per 24-hour urine test or the Cockcroft-Gault formula

Exclusion Criteria:

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
History of progressive multifocal leukoencephalopathy (PML)
Active pneumonitis or interstitial lung disease
Prior solid organ or allogeneic stem cell transplantation
History of known or suspected hemophagocytic lymphohistiocytosis (HLH)
Active, known or suspected autoimmune disease. The following are exceptions:

Vitiligo
Psoriasis not requiring systemic treatment
Hemolytic anemia associated with the lymphoma
Type I diabetes mellitus, if adequately controlled with therapy
Thyroid disease, if adequately controlled with therapy
Conditions not expected to recur in the absence of an external trigger (such exceptions should be discussed with the study PI)
Active history of:

Hepatitis B (HBV) or C (HCV) infection. Patients with past HBV infection (defined as negative HBsAg and positive hepatitis B core antibody \[HBcAb\]) are eligible if HBV DNA is undetectable. Patients who are positive for HCV antibody are eligible if polymerase chain reaction (PCR) is negative for HCV RNA
HIV positive
History of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association class III-IV within 6 months prior to day 1 of protocol therapy
Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Study Design

Enrollment

23 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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

See Detailed Description.

Interventions

Biospecimen Collection

Undergo collection of blood samples

Brentuximab Vedotin

Given IV

Computed Tomography

Undergo PET/CT

Dacarbazine

Given IV

Echocardiography Test

Undergo ECHO

Gemcitabine

Given IV

Pembrolizumab

Given IV

Physical Performance Testing

Ancillary studies

Positron Emission Tomography

Undergo PET/CT

Pulmonary Function Test

Ancillary studies

Primary outcome measure

Complete metabolic response (CMR) to pembrolizumab and gemcitabine (P-G) [ Time Frame: During/after cycles 1-8 of P-G (cycle length = 21 days), before initiation of salvage or maintenance therapy or non-protocol lymphoma therapy ]

Central Contacts and Locations

Locations

City of Hope Medical Center

Recruiting

Duarte, California, United States, 91010

Contacts

Matthew Mei

626-218-2405 mamei@coh.org

Principal Investigator:

Matthew Mei

More Information

Sponsor

City of Hope Medical Center

Last update posted

Aug 20, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by City of Hope Medical Center on 2026-08-20.