PET Adapted Brentuximab Vedotin and Pembrolizumab in Combination With Doxorubicin and Dacarbazine in Classic Hodgkin Lymphoma

NCT05922904 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2022-0492NCI-2023-05028
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

To learn about the effects of brentuximab vedotin and pembrolizumab in combination with doxorubicin and dacarbazine when given to patients who have Stage II cHL with bulky mediastinal disease or advanced cHL (Stage III or IV) and who have not received treatment for the disease.

Conditions

Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  through study completion; an average of 1 year.

Study Arms (3)

Part A: Pembrolizumab and Brentuximab +AD

EXPERIMENTAL

Drug: Brentuximab vedotin; Drug: Doxorubicin Hydrochloride; Drug: Pembrolizumab; Drug: Dacarbazine

Part B: De-Escalation

EXPERIMENTAL

Drug: Brentuximab vedotin; Drug: Doxorubicin Hydrochloride; Drug: Pembrolizumab; Drug: Dacarbazine

Part C: Standard Risk Arm

EXPERIMENTAL

Drug: Brentuximab vedotin; Drug: Doxorubicin Hydrochloride; Drug: Pembrolizumab; Drug: Dacarbazine

Interventions

Brentuximab vedotin DRUG

Given by IV (vein)

Part A: Pembrolizumab and Brentuximab +AD; Part B: De-Escalation; Part C: Standard Risk Arm

Doxorubicin Hydrochloride DRUG

Given by IV (vein)

Also known as: Adriamycin PFS®, Adriamycin RDF™, Adriamycin®, Rubex®

Part A: Pembrolizumab and Brentuximab +AD; Part B: De-Escalation; Part C: Standard Risk Arm

Pembrolizumab DRUG

Given by IV (vein)

Also known as: SGN-35, Adcetris

Part A: Pembrolizumab and Brentuximab +AD; Part B: De-Escalation; Part C: Standard Risk Arm

Dacarbazine DRUG

Given by IV (vein)

Also known as: DTIC-Dome®

Part A: Pembrolizumab and Brentuximab +AD; Part B: De-Escalation; Part C: Standard Risk Arm

Eligibility Criteria

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

You may qualify if:

• Treatment-naïve, HL subjects with Ann Arbor stage III, IV, or stage II with bulky disease (\>10 cm).
• Histologically confirmed cHL according to the current World Health Organization Classification (nodular sclerosis, mixed cellularity, lymphocyte rich, lymphocyte depleted, classical HL, or not otherwise specified). a. Subjects enrolling must submit a tumor block for analysis. Availability of tissue must be confirmed prior to enrollment.
• Bidimensional measurable disease as documented by PET/CT or CT imaging. Must have at least one lesion \>15 mm (1.5 cm) in the longest diameter on cross-sectional imaging, measurable in 2 perpendicular dimensions on CT (or MRI), and FDG avid by PET.
• Age 18 years or older.
• An Eastern Cooperative Oncology Group (ECOG) performance status zero, or one.
• Subjects of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (β-hCG) pregnancy test result within 7 days prior to the first dose of brentuximab vedotin. Subjects with false positive results and documented verification that the subject is not pregnant are eligible for participation. Subjects of non-childbearing potential are those who are postmenopausal \>1 year or who have had a bilateral oophorectomy or hysterectomy.
• If sexually active in a way that could result in pregnancy, subjects of childbearing potential must agree to use 2 effective contraception methods during the study and for 7 months following the last dose of study drug. Subjects who can father children and have partners of childbearing potential must agree to use 2 effective contraception methods during the study and for 7 months following the last dose of study drug. Subjects who can father children must also be willing to refrain from sperm donation during this time.
• The subject or the subject's legally acceptable representative must provide written informed consent. Cognitive ability will be assessed according to policy CLN0547.
• The following baseline laboratory data:
• absolute neutrophil count ≥1500/μL unless there is known HL marrow involvement
• platelet count ≥75,000/μL
• serum bilirubin ≤1.5 x upper limit of normal (ULN) or ≤3 x ULN for subjects with Gilbert's disease
• estimated glomerular filtration rate (GFR) ≥30 mL/min/1.73 m2 using the Modification of Diet in Renal Disease (MDRD) study equation as applicable
• alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 x ULN or ≤5 x ULN if there is documented hepatic involvement of HL
• hemoglobin ≥8 g/dL

You may not qualify if:

• Nodular lymphocyte predominant HL.
• History of another malignancy within 3 years before the first dose of study drug or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death (e.g., 5-year OS ≥90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer. Subjects with nonmelanoma skin cancer, localized prostate cancer, or carcinoma in situ of any type are not excluded if they have undergone complete resection.
• Prior immunosuppressive chemotherapy, therapeutic radiation, or any immunotherapy (e.g., immunoglobulin replacement, other monoclonal antibody therapies) within 4 weeks of first study drug dose, unless underlying disease has progressed on treatment.
• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
• Active cerebral/meningeal disease related to the underlying malignancy, including signs or symptoms of progressive multifocal leukoencephalopathy (PML) or history of PML. Subjects with a history of cerebral/meningeal disease related to the underlying malignancy are allowed if prior CNS disease has been treated.
• Any active Grade 3 or higher (per the National Cancer Institute's Common Terminology Criteria for Adverse Events \[NCI CTCAE\] Version 4.03) viral, bacterial, or fungal infection within 1 week prior to the first dose of study drug. Routine antimicrobial prophylaxis is permitted.
• Current therapy with other systemic anti-neoplastic or investigational agents.
• Planned consolidative radiotherapy.
• Active interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
• Grade 3 or higher pulmonary disease unrelated to underlying malignancy.
• Idiopathic interstitial pneumonia or diffusing capacity of the lung for carbon monoxide (adjusted for hemoglobin) \<50% predicted.
• Documented 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 their first dose of brentuximab vedotin. See Appendix E
• Subjects with Child-Pugh class B or C hepatic impairment.
• Other serious underlying medical condition that, in the opinion of the investigator, would impair the subject's ability to receive or tolerate the planned treatment and follow-up.
• Symptomatic neurologic disease compromising normal activities of daily living or requiring medications. See Appendix G

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator
• Seagen Inc.: collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Kreuzberger N, Goldkuhle M, von Tresckow B, Kobe C, Sickinger MT, Monsef I, Skoetz N. Positron emission tomography-adapted therapy for first-line treatment in adults with Hodgkin lymphoma. Cochrane Database Syst Rev. 2025 Mar 26;3(3):CD010533. doi: 10.1002/14651858.CD010533.pub3.

  PMID: 40135712 DERIVED

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Hodgkin Disease

Interventions

Brentuximab Vedotin; Doxorubicin; pembrolizumab; Dacarbazine

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)

Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Hun Lee, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 20, 2023
• First Posted: June 28, 2023
• Study Start: December 14, 2023
• Primary Completion (Estimated): October 30, 2027
• Study Completion (Estimated): October 30, 2027
• Last Updated: April 15, 2026

Record last verified: 2026-04

Locations

US (1)