Clinical Trial of Brentuximab Vedotin in Classical Hodgkin Lymphoma

Multiple Part Clinical Trial of Brentuximab Vedotin in Classical Hodgkin Lymphoma Subjects

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Hodgkin Lymphoma
• Intervention / Treatment: Drug: brentuximab vedotin; Drug: doxorubicin; Drug: vinblastine; Drug: dacarbazine; Drug: G-CSF; Drug: nivolumab

Detailed Description

This study will have three parts.

Part A of the study is designed to evaluate the incidence of febrile neutropenia, efficacy, and dose intensity in participants with advanced stage classical Hodgkin lymphoma (cHL) receiving granulocyte colony stimulating factor primary prophylaxis (G-PP) administration during treatment with frontline A+AVD. In Part A, participants will be treated with granulocyte colony stimulating factor (G-CSF) following every dose of A+AVD for 6 cycles of treatment. Participants will be treated using institutional standard of care practices for the majority of treatment decisions.

Part B is designed to evaluate the combination of brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine (AN+AD) as frontline treatment in participants with advanced cHL. In Part B, participants will be given AN+AD combination for 6 cycles of treatment. This part of the trial will look at whether this combination of drugs is effective and tolerable in participants with Stage II with bulky mediastinal disease and Stage III or IV cHL.

Part C is designed to evaluate AN+AD as frontline treatment in participants with early stage cHL. In Part C, participants will be given AN+AD combination for 4 cycles of treatment. This part of the trial will look at whether this combination of drugs is effective and tolerable in participants with Stage I or II cHL with non-bulky mediastinal disease.

• Study Type: Interventional
• Enrollment (Actual): 255
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Other
    • Adelaide, Other, Australia, 5000
      • Royal Adelaide Hospital
    • Ballarat, Other, Australia, 3350
      • Ballarat Regional Integrated Cancer Care
    • Clayton, Other, Australia, 3168
      • Monash Medical Centre
    • Victoria, Other, Australia, 3002
      • Epworth Healthcare
• Czechia
  • Other
    • Hradec Kralove, Other, Czechia, 500 05
      • Fakultni nemocnice Hradec Kralove-oddeleni klinicke hematologie
    • Praha 10, Other, Czechia, 100 34
      • Fakultni nemocnice Kralovske Vinohrady
• Italy
  • Other
    • Brescia, Other, Italy, 25123
      • Azienda Ospedaliera Spedali Civili di Brescia
    • Pavia, Other, Italy, 27100
      • IRCSS Policlinico San Matteo
    • Siena, Other, Italy, 53100
      • Azienda Ospedaliera Universitaria Senese
    • Torino, Other, Italy, 10126
      • Azienda Ospedaliera Citta Della Salute E Della Scienza Di Torino
• Poland
  • Other
    • Krakow, Other, Poland, 30-727
      • Pratia MCM Krakow
• Spain
  • Other
    • Barcelona, Other, Spain, 08003
      • Hospital del Mar
    • Barcelona, Other, Spain, 08908
      • Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)
    • Barcelona, Other, Spain, 08035
      • Hospital Universitari Vall d'Hebron
    • Girona, Other, Spain, 17007
      • Hospital Universitario de Girona Doctor Josep Trueta
    • Madrid, Other, Spain, 28040
      • Hospital Universitario Fundacion Jimenez Diaz
    • Madrid, Other, Spain, 28041
      • Hospital Universitario 12 de Octubre
    • Majadahonda, Other, Spain, 28222
      • Hospital Puerta de Hierro Majadahonda
    • Oviedo, Other, Spain, 33011
      • Hospital Universitario Central de Asturias
    • Salamanca, Other, Spain, 37007
      • Hospital Clínico Universitario de Salamanca
    • Valencia, Other, Spain, 46026
      • Hospital Universitari i Politecnic La Fe de Valencia
• United States
  • California
    • Fountain Valley, California, United States, 92708
      • Compassionate Care Research Group
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Rocky Mountain Cancer Centers - Aurora
    • Colorado Springs, Colorado, United States, 80909
      • University of Colorado Health Memorial Hospital
    • Denver, Colorado, United States, 80218
      • Cancer Centers of Colorado - Denver
    • Fort Collins, Colorado, United States, 80528
      • Poudre Valley Health System (PVHS)
    • Grand Junction, Colorado, United States, 81501
      • SCL Health - St. Mary's Hospital & Medical Center
  • Florida
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute at Baptist Health, Inc.
    • Saint Petersburg, Florida, United States, 33705
      • Florida Cancer Specialists - North Region
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Cardinal Bernardin Cancer Center / Loyola University Medical Center
    • Niles, Illinois, United States, 60714
      • Illinois Cancer Specialists
    • Peoria, Illinois, United States, 61615
      • Illinois Cancer Care
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute / Wayne State University
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Minnesota Oncology Hematology P.A.
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University in St Louis
  • New Jersey
    • Brick, New Jersey, United States, 08724
      • New Jersey Hematology Oncology Associates, LLC
    • Freehold, New Jersey, United States, 07728
      • Regional Cancer Care Associates - Freehold
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • Howell, New Jersey, United States, 07731
      • Regional Cancer Care Associates - Howell
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center/ Carol G. Simon Cancer Center
    • Mount Holly, New Jersey, United States, 08060
      • Regional Cancer Care Associates - Mount Holly
    • Somerville, New Jersey, United States, 08876
      • Regional Cancer Care Associates - Central Jersey
    • Sparta, New Jersey, United States, 07871
      • Regional Cancer Care Associates - Sparta
  • New York
    • Albany, New York, United States, 12208
      • New York Oncology Hematology, P.C.
    • Mount Kisco, New York, United States, 10549-3412
      • CareMount Medical Group
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
    • Purchase, New York, United States, 10577
      • Clinical Research Alliance - Abraham Mittelman, MD, LLC
    • Westbury, New York, United States, 11590
      • Clinical Research Alliance - Morton Coleman, MD
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Medical Center / Wake Forest University
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic, The
    • Toledo, Ohio, United States, 43623
      • Toledo Clinic Cancer Center
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Willamette Valley Cancer Institute and Research Center
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina/Hollings Cancer Center
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology-Nashville/Sarah Cannon Research Institute
  • Texas
    • Austin, Texas, United States, 78705
      • Texas Oncology - Austin Midtown
    • Dallas, Texas, United States, 75230
      • Texas Oncology - Medical City Dallas
    • Flower Mound, Texas, United States, 75028
      • Texas Oncology - Flower Mound
    • Fort Sam Houston, Texas, United States, 78234
      • Brooke Army Medical Center
    • Fort Worth, Texas, United States, 76104
      • Texas Oncology - Fort Worth 12th Avenue
    • Houston, Texas, United States, 77030-4095
      • MD Anderson Cancer Center / University of Texas
    • San Antonio, Texas, United States, 78240
      • Texas Oncology - San Antonio Medical Center
    • Tyler, Texas, United States, 75702
      • Texas Oncology - Northeast Texas
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists, PC
    • Salem, Virginia, United States, 24153
      • Oncology and Hematology Assoc of SW VA DBA Blue Ridge Cancer Care
  • Washington
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology and Oncology
    • Olympia, Washington, United States, 98506
      • Vista Oncology Inc PS
    • Seattle, Washington, United States, 98109-1023
      • Seattle Cancer Care Alliance / University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• Previous treatment with brentuximab vedotin
• Participants who are pregnant or breastfeeding
• Other serious condition that would impair the participant's ability to receive or tolerate the planned treatment and follow-up

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: A+AVD; 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; 1.2 mg/kg by IV infusion; Other Names: Adcetris; SGN-35; Drug: doxorubicin; 25 mg/m^2 by IV infusion; Drug: vinblastine; 6 mg/m^2 by IV infusion; Drug: dacarbazine; 375 mg/m^2 by IV infusion; Drug: G-CSF; Granulocyte colony stimulating factor (G-CSF) primary prophylaxis administered 24-36 hours after each dose of A+AVD; Other Names: filgrastim; pegfilgrastim
Experimental: Part B: AN+AD; 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; 1.2 mg/kg by IV infusion; Other Names: Adcetris; SGN-35; Drug: doxorubicin; 25 mg/m^2 by IV infusion; Drug: dacarbazine; 375 mg/m^2 by IV infusion; Drug: nivolumab; 240 mg by IV infusion; Other Names: Opdivo
Experimental: Part C: AN+AD; 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; 1.2 mg/kg by IV infusion; Other Names: Adcetris; SGN-35; Drug: doxorubicin; 25 mg/m^2 by IV infusion; Drug: dacarbazine; 375 mg/m^2 by IV infusion; Drug: nivolumab; 240 mg by IV infusion; Other Names: Opdivo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 (Parts B and C)	CR rate at EOT is defined as the percentage of subjects with CR at EOT, according to the Lugano Classification Revised Staging System for malignant lymphoma (Cheson 2014) with the incorporation of LYRIC (Cheson 2016), in subjects with previously untreated cHL.	7.8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Refractory Disease Rate (Part A)	The primary refractory disease rate is defined as the percentage of participants with less than complete response or relapse within 3 months of EOT, according to the Lugano Classification Revised Staging System for nodal non-Hodgkin and Hodgkin lymphomas	10.2 months
Complete Response Rate (Part A)	The complete response rate is defined as the percentage of participants with CR at EOT according to the Lugano Classification Revised Staging System for nodal non-Hodgkin and Hodgkin lymphomas (Cheson 2014).	7.2 months
Physician-reported Progression Free Survival (PFS) (Part A)	The physician-reported PFS rate at 2 years is estimated based on Kaplan-Meier methodology.	24 months
Subsequent Anticancer Therapy Utilization Rate (Part A)	Number of participants with subsequent anticancer therapy	33.8 months
Actual Dose Intensity: Brentuximab Vedotin (Part A)		6.5 months
Actual Dose Intensity: Doxorubicin, Vinblastine, Dacarbazine (Part A)		6.5 months
Relative Dose Intensity (Part A)		6.5 months
Rate of Dose Reduction and Delays: Brentuximab Vedotin (Part A)		6.5 months
Rate of Dose Reduction and Delays: Doxorubicin (Part A)		6.5 months
Rate of Dose Reduction and Delays: Vinblastine (Part A)		6.5 months
Rate of Dose Reduction and Delays: Dacarbazine (Part A)		6.5 months
Incidence of Adverse Events (Parts B and C)		8.9 months
Incidence of Laboratory Abnormalities (Parts B and C)	Laboratory values were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE version 4.03).	8.9 months
Overall Response Rate (ORR) at EOT (Parts B and C)	ORR is defined as the proportion of participants with CR or partial response (PR) at EOT according to the Lugano Classification Revised Staging System for malignant lymphoma (Cheson 2014) with the incorporation of LYRIC (Cheson 2016) in subjects with previously untreated cHL.	7.8 months

Collaborators and Investigators

• Sponsor: Seagen Inc.
• Collaborators: Bristol-Myers Squibb
• Investigators: Study Director: Linda Ho, MD, Seagen Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2019
• Primary Completion (Actual): November 7, 2022
• Study Completion (Estimated): June 7, 2026

Study Registration Dates

• First Submitted: August 22, 2018
• First Submitted That Met QC Criteria: August 22, 2018
• First Posted (Actual): August 24, 2018

Study Record Updates

• Last Update Posted (Estimated): February 21, 2024
• Last Update Submitted That Met QC Criteria: February 16, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Nivolumab; Doxorubicin; Brentuximab vedotin; Vinblastine; Dacarbazine; Seattle Genetics
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Hodgkin Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Immune Checkpoint Inhibitors; Immunoconjugates; Immunotoxins; Nivolumab; Doxorubicin; Dacarbazine; Brentuximab Vedotin; Vinblastine
• Other Study ID Numbers: SGN35-027

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No