Clinical Trial of Brentuximab Vedotin in Classical Hodgkin Lymphoma

NCT03646123 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: SGN35-027
• Study Type: interventional
• Target: 255
• Locations: 6 countries
• Sites: 76

Brief Summary

This trial will study two treatment combinations for classical Hodgkin lymphoma (cHL). This trial will find out if these two treatment combinations work to treat cHL. It will also find out what side effects occur. A side effect is anything the drug does besides treating cancer. This study will have three parts (Parts A, B, and C). The drugs used in Part A are a combination of targeted anticancer drug (brentuximab vedotin) and three chemotherapy drugs (doxorubicin, vinblastine, and dacarbazine). These four drugs are called "A+AVD." Participants will be treated with granulocyte colony stimulating factor (G-CSF) following every dose of A+AVD for 6 cycles of treatment (12 doses). Part A will look at whether the A+AVD drug combination reduces the number of participants who experience the side effect of febrile neutropenia. Febrile neutropenia is a very low white blood cell count and a fever, which can be life threatening. Parts B and C will use drug combination of brentuximab vedotin, plus nivolumab, doxorubicin, and dacarbazine. These four drugs are called "AN+AD." Parts B and C will study how well the drugs work to treat cHL and what side effects they cause.

Conditions

Hodgkin Lymphoma

Keywords

Brentuximab vedotin; Doxorubicin; Vinblastine; Dacarbazine; Nivolumab; Seattle Genetics

Outcome Measures

Primary Outcomes (2)

• Febrile Neutropenia (FN) Rate (Part A)

  The FN rate is defined as the number of participants who experience treatment-emergent FN.

  7.5 months

• Complete Response (CR) Rate at EOT (Parts B and C)

  CR rate at EOT is defined as the percentage of participants with CR at EOT, according to the Lugano Classification Revised Staging System for malignant lymphoma (Cheson 2014) with the incorporation of Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) (Cheson 2016), in participants with previously untreated cHL.

  7.8 months

Secondary Outcomes (20)

• Number of Participants With Adverse Events of Clinical Interest (AECI) (Part A)

  Approximately up to 7.5 months

• Primary Refractory Disease Rate (Part A)

  10.2 months

• Complete Response Rate (Part A)

  7.2 months

• Physician-reported Progression Free Survival (PFS) (Part A)

  24 months

• Number of Participants With Subsequent Anticancer Therapy Utilization (Part A)

  33.8 months

Study Arms (3)

Part A: A+AVD

EXPERIMENTAL

Brentuximab vedotin (A) plus doxorubicin (+A), vinblastine (V), and dacarbazine (D) administered by intravenous (IV) infusion in participants with advanced stage classical Hodgkin lymphoma (cHL) during each treatment cycle.

Drug: brentuximab vedotin; Drug: doxorubicin; Drug: vinblastine; Drug: dacarbazine; Drug: G-CSF

Part B: AN+AD

EXPERIMENTAL

Brentuximab vedotin (A) plus nivolumab (N), doxorubicin (+A), and dacarbazine (D) administered separately by IV infusion in participants with Stage II bulky mediastinal disease and Stage III or IV cHL during each treatment cycle.

Drug: brentuximab vedotin; Drug: doxorubicin; Drug: dacarbazine; Drug: nivolumab

Part C: AN+AD

EXPERIMENTAL

Brentuximab vedotin (A) plus nivolumab (N), doxorubicin (+A), and dacarbazine (D) administered separately by IV infusion in participants with Stage I or II cHL with non-bulky mediastinal disease during each treatment cycle.

Drug: brentuximab vedotin; Drug: doxorubicin; Drug: dacarbazine; Drug: nivolumab

Interventions

brentuximab vedotin DRUG

1.2 mg/kg by IV infusion

Also known as: Adcetris, SGN-35

Part A: A+AVD; Part B: AN+AD; Part C: AN+AD

doxorubicin DRUG

25 mg/m\^2 by IV infusion

Part A: A+AVD; Part B: AN+AD; Part C: AN+AD

vinblastine DRUG

6 mg/m\^2 by IV infusion

Part A: A+AVD

dacarbazine DRUG

375 mg/m\^2 by IV infusion

Part A: A+AVD; Part B: AN+AD; Part C: AN+AD

G-CSF DRUG

Granulocyte colony stimulating factor (G-CSF) primary prophylaxis administered 24-36 hours after each dose of A+AVD

Also known as: filgrastim, pegfilgrastim

Part A: A+AVD

nivolumab DRUG

240 mg by IV infusion

Also known as: Opdivo

Part B: AN+AD; Part C: AN+AD

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Treatment-naïve, classic Hodgkin lymphoma (cHL) participants
• Participants enrolling in Part A of the study must have Ann Arbor Stage III or IV disease
• Participants enrolling in Part B of the study must have Ann Arbor Stage I or II cH: with bulky mediastinal disease, or Stage III or IV
• Participants enrolling in Part C of the study must have Ann Arbor Stage I or II cHL without bulky disease
• Histologically confirmed cHL according to the current World Health Organization (WHO) Classification
• Bidimensional measurable disease as documented by PET/CT or CT imaging
• Age 12 years or older in the United States. For regions outside of the US, participants must 18 years or older.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

You may not qualify if:

• Nodular lymphocyte predominant HL
• History of another malignancy within 3 years of the first dose of study drug or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk or metastasis or death. Participants 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 within 4 weeks of the first study drug dose
• 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
• Any active Grade 3 or higher viral, bacterial, or fungal infection within two weeks of the first dose of study drug (Grade 3 defined by the National Cancer Institute's Common Terminology Criteria for Adverse Events, NCI CTCAE Version 4.03)
• Current therapy with other systemic anti-neoplastic or investigational agents
• Planned consolidative radiotherapy (Parts B and C only)
• Active interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity (Parts B and C only)
• Grade 3 or higher pulmonary disease unrelated to underlying malignancy
• Documented history of idiopathic interstitial pneumonia or diffusing capacity of the lung for carbon monoxide \<50% predicted
• History of a cerebral vascular event within 6 months of first dose of study drug
• Child-Pugh B or C hepatic impairment
• Grade 2 or higher peripheral sensory or motor neuropathy
• Participants with acute or chronic graft-versus-host-disease (GvHD) or receiving immunosuppressive therapy as treatment or as prophylaxis against GvHD

Sponsors & Collaborators

• Seagen Inc.: lead
• Bristol-Myers Squibb: collaborator

Study Sites (76)

Los Angeles Cancer Network / Compassionate Care Research Group

Fountain Valley, California, 92708, United States

Location

Rocky Mountain Cancer Centers - Aurora

Aurora, Colorado, 80012, United States

Location

University of Colorado Health Memorial Hospital

Colorado Springs, Colorado, 80909, United States

Location

Cancer Centers of Colorado - Denver

Denver, Colorado, 80218, United States

Location

Poudre Valley Health System (PVHS)

Fort Collins, Colorado, 80528, United States

Location

SCL Health - St. Mary's Hospital & Medical Center

Grand Junction, Colorado, 81501, United States

Location

Miami Cancer Institute at Baptist Health, Inc.

Miami, Florida, 33176, United States

Location

Florida Cancer Specialists - North Region

St. Petersburg, Florida, 33705, United States

Location

Cardinal Bernardin Cancer Center / Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Illinois Cancer Specialists

Niles, Illinois, 60714, United States

Location

Illinois Cancer Care

Peoria, Illinois, 61615, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Institute / Wayne State University

Detroit, Michigan, 48201, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Minnesota Oncology Hematology P.A.

Edina, Minnesota, 55435, United States

Location

Washington University in St Louis

St Louis, Missouri, 63110, United States

Location

New Jersey Hematology Oncology Associates, LLC

Brick, New Jersey, 08724, United States

Location

Regional Cancer Care Associates - Freehold

Freehold, New Jersey, 07728, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Regional Cancer Care Associates - Howell

Howell Township, New Jersey, 07731, United States

Location

Morristown Medical Center/ Carol G. Simon Cancer Center

Morristown, New Jersey, 07960, United States

Location

Regional Cancer Care Associates - Mount Holly

Mount Holly, New Jersey, 08060, United States

Location

Regional Cancer Care Associates - Central Jersey

Somerville, New Jersey, 08876, United States

Location

Regional Cancer Care Associates - Sparta

Sparta, New Jersey, 07871, United States

Location

New York Oncology Hematology, P.C.

Albany, New York, 12208, United States

Location

CareMount Medical Group

Mount Kisco, New York, 10549-3412, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Clinical Research Alliance - Abraham Mittelman, MD, LLC

Purchase, New York, 10577, United States

Location

Clinical Research Alliance - Morton Coleman, MD

Westbury, New York, 11590, United States

Location

Wake Forest Baptist Medical Center / Wake Forest University

Winston-Salem, North Carolina, 27157, United States

Location

Oncology Hematology Care

Cincinnati, Ohio, 45242, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic, The

Cleveland, Ohio, 44195, United States

Location

Toledo Clinic Cancer Center

Toledo, Ohio, 43623, United States

Location

Willamette Valley Cancer Institute and Research Center

Eugene, Oregon, 97401, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

Medical University of South Carolina/Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

University of Tennessee

Knoxville, Tennessee, 37920, United States

Location

Tennessee Oncology-Nashville/Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Texas Oncology - Austin Midtown

Austin, Texas, 78705, United States

Location

Texas Oncology - Medical City Dallas

Dallas, Texas, 75230, United States

Location

Texas Oncology - Flower Mound

Flower Mound, Texas, 75028, United States

Location

Brooke Army Medical Center

Fort Sam Houston, Texas, 78234, United States

Location

Texas Oncology - Fort Worth 12th Avenue

Fort Worth, Texas, 76104, United States

Location

MD Anderson Cancer Center / University of Texas

Houston, Texas, 77030-4095, United States

Location

Texas Oncology - San Antonio Medical Center

San Antonio, Texas, 78240, United States

Location

Texas Oncology - Northeast Texas

Tyler, Texas, 75702, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Oncology and Hematology Assoc of SW VA DBA Blue Ridge Cancer Care

Salem, Virginia, 24153, United States

Location

Kadlec Clinic Hematology and Oncology

Kennewick, Washington, 99336, United States

Location

Vista Oncology Inc PS

Olympia, Washington, 98506, United States

Location

Seattle Cancer Care Alliance / University of Washington

Seattle, Washington, 98109-1023, United States

Location

Royal Adelaide Hospital

Adelaide, Other, 5000, Australia

Location

Ballarat Regional Integrated Cancer Care

Ballarat, Other, 3350, Australia

Location

Monash Medical Centre

Clayton, Other, 3168, Australia

Location

Epworth Healthcare

Victoria, Other, 3002, Australia

Location

Fakultni nemocnice Hradec Kralove-oddeleni klinicke hematologie

Hradec Králové, Other, 500 05, Czechia

Location

Fakultni Nemocnice Kralovske Vinohrady

Prague, Other, 100 34, Czechia

Location

Azienda Ospedaliera Spedali Civili di Brescia

Brescia, Other, 25123, Italy

Location

IRCSS Policlinico San Matteo

Pavia, Other, 27100, Italy

Location

Azienda Ospedaliera Universitaria Senese

Siena, Other, 53100, Italy

Location

Azienda Ospedaliera Citta della Salute e della Scienza di Torino

Torino, Other, 10126, Italy

Location

Pratia MCM Krakow

Krakow, Other, 30-727, Poland

Location

Hospital del Mar

Barcelona, Other, 08003, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, Other, 08035, Spain

Location

Institut Catala d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)

Barcelona, Other, 08908, Spain

Location

Hospital Universitario de Girona Doctor Josep Trueta

Girona, Other, 17007, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz

Madrid, Other, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Other, 28041, Spain

Location

Hospital Puerta de Hierro Majadahonda

Majadahonda, Other, 28222, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, Other, 33011, Spain

Location

Hospital Clinico Universitario de Salamanca

Salamanca, Other, 37007, Spain

Location

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, Other, 46026, Spain

Location

Related Publications (2)

• Abramson JS, Straus DJ, Bartlett NL, Burke JM, Lynch RC, Domingo-Domenech E, Hess BT, Schuster SR, Linhares Y, Gandhi MD, Shah HR, Jurczak W, Re A, Hahn U, Prince HM, Guo W, Davis G, Ho L, Fanale M, Yasenchak CA, Lee HJJ. Brentuximab Vedotin and Nivolumab in Combination With Chemotherapy for Nonbulky, Early-Stage Classical Hodgkin Lymphoma. Blood. 2025 Dec 29:blood.2025030190. doi: 10.1182/blood.2025030190. Online ahead of print.

  PMID: 41460964 DERIVED

• Lee HJ, Ramchandren R, Friedman J, Melear J, Flinn IW, Burke JM, Linhares Y, Gonzales P, Peterson M, Raval M, Chintapatla R, Feldman TA, Yimer H, Islas-Ohlmayer M, Patel A, Metheny L, Dean A, Rana V, Gandhi MD, Renshaw J, Ho L, Fanale MA, Guo W, Yasenchak CA. Brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine for advanced-stage classical Hodgkin lymphoma. Blood. 2025 Jan 16;145(3):290-299. doi: 10.1182/blood.2024024681.

  PMID: 39622165 DERIVED

MeSH Terms

Conditions

Hodgkin Disease

Interventions

Brentuximab Vedotin; Doxorubicin; Vinblastine; Dacarbazine; Granulocyte Colony-Stimulating Factor; Filgrastim; pegfilgrastim; Nivolumab

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; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Biological Factors

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Medical Monitor

  Seagen Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: August 22, 2018
• First Posted: August 24, 2018
• Study Start: January 28, 2019
• Primary Completion: November 7, 2022
• Study Completion: August 23, 2024
• Last Updated: August 28, 2025
• Results First Posted: December 21, 2023

Record last verified: 2025-08

Locations

US (55); AU (4); IT (4); ES (10); CZ (2); PL (1)