Clinical Trial of Brentuximab Vedotin in Classical Hodgkin Lymphoma
- Conditions
- Hodgkin Lymphoma
- Interventions
- Registration Number
- NCT03646123
- Lead Sponsor
- Seagen Inc.
- 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.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 255
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part A: A+AVD dacarbazine 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. Part A: A+AVD brentuximab vedotin 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. Part B: AN+AD brentuximab vedotin 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. Part B: AN+AD doxorubicin 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. Part A: A+AVD doxorubicin 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. Part A: A+AVD vinblastine 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. Part C: AN+AD nivolumab 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. Part B: AN+AD dacarbazine 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. Part C: AN+AD dacarbazine 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. Part A: A+AVD G-CSF 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. Part B: AN+AD nivolumab 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. Part C: AN+AD brentuximab vedotin 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. Part C: AN+AD doxorubicin 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.
- Primary Outcome Measures
Name Time Method Febrile Neutropenia (FN) Rate (Part A) 7.5 months The FN rate is defined as the number of participants who experience treatment-emergent FN.
Complete Response (CR) Rate (Parts B and C) 7.8 months 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.
- Secondary Outcome Measures
Name Time Method Physician-reported Progression Free Survival (PFS) (Part A) 24 months The physician-reported PFS rate at 2 years is estimated based on Kaplan-Meier methodology.
Actual Dose Intensity: Doxorubicin, Vinblastine, Dacarbazine (Part A) 6.5 months Rate of Dose Reduction and Delays: Brentuximab Vedotin (Part A) 6.5 months Rate of Dose Reduction and Delays: Vinblastine (Part A) 6.5 months Overall Response Rate (ORR) at EOT (Parts B and C) 7.8 months 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.
Relative Dose Intensity (Part A) 6.5 months Rate of Dose Reduction and Delays: Dacarbazine (Part A) 6.5 months Subsequent Anticancer Therapy Utilization Rate (Part A) 33.8 months Number of participants with subsequent anticancer therapy
Incidence of Adverse Events (Parts B and C) 8.9 months Complete Response Rate (Part A) 7.2 months 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).
Actual Dose Intensity: Brentuximab Vedotin (Part A) 6.5 months Rate of Dose Reduction and Delays: Doxorubicin (Part A) 6.5 months Incidence of Laboratory Abnormalities (Parts B and C) 8.9 months Laboratory values were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE version 4.03).
Primary Refractory Disease Rate (Part A) 10.2 months 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
Trial Locations
- Locations (76)
Texas Oncology - Flower Mound
🇺🇸Flower Mound, Texas, United States
Clinical Research Alliance - Abraham Mittelman, MD, LLC
🇺🇸Purchase, New York, United States
Fakultni Nemocnice Kralovske Vinohrady
🇨🇿Praha 10, Other, Czechia
Toledo Clinic Cancer Center
🇺🇸Toledo, Ohio, United States
New York Oncology Hematology, P.C.
🇺🇸Albany, New York, United States
Minnesota Oncology Hematology P.A.
🇺🇸Edina, Minnesota, United States
Willamette Valley Cancer Institute and Research Center
🇺🇸Eugene, Oregon, United States
Fakultni nemocnice Hradec Kralove-oddeleni klinicke hematologie
🇨🇿Hradec Kralove, Other, Czechia
Regional Cancer Care Associates - Freehold
🇺🇸Freehold, New Jersey, United States
Vista Oncology Inc PS
🇺🇸Olympia, Washington, United States
Epworth Healthcare
🇦🇺Victoria, Other, Australia
Monash Medical Centre
🇦🇺Clayton, Other, Australia
Hospital Puerta de Hierro Majadahonda
🇪🇸Majadahonda, Other, Spain
Hospital Universitario Fundacion Jimenez Diaz
🇪🇸Madrid, Other, Spain
Pratia MCM Krakow
🇵🇱Krakow, Other, Poland
Texas Oncology - Austin Midtown
🇺🇸Austin, Texas, United States
Mount Sinai Medical Center
🇺🇸New York, New York, United States
Hospital del Mar
🇪🇸Barcelona, Other, Spain
Brooke Army Medical Center
🇺🇸Fort Sam Houston, Texas, United States
Kadlec Clinic Hematology and Oncology
🇺🇸Kennewick, Washington, United States
Hospital Universitario Central de Asturias
🇪🇸Oviedo, Other, Spain
Ballarat Regional Integrated Cancer Care
🇦🇺Ballarat, Other, Australia
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Other, Spain
Hospital Universitario de Girona Doctor Josep Trueta
🇪🇸Girona, Other, Spain
Hospital Universitari i Politecnic La Fe de Valencia
🇪🇸Valencia, Other, Spain
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic, The
🇺🇸Cleveland, Ohio, United States
MD Anderson Cancer Center / University of Texas
🇺🇸Houston, Texas, United States
Texas Oncology - San Antonio Medical Center
🇺🇸San Antonio, Texas, United States
Huntsman Cancer Institute/University of Utah
🇺🇸Salt Lake City, Utah, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
New Jersey Hematology Oncology Associates, LLC
🇺🇸Brick, New Jersey, United States
University of Tennessee
🇺🇸Knoxville, Tennessee, United States
Regional Cancer Care Associates - Central Jersey
🇺🇸Somerville, New Jersey, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Morristown Medical Center/ Carol G. Simon Cancer Center
🇺🇸Morristown, New Jersey, United States
Regional Cancer Care Associates - Sparta
🇺🇸Sparta, New Jersey, United States
Regional Cancer Care Associates - Howell
🇺🇸Howell, New Jersey, United States
Tennessee Oncology-Nashville/Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Regional Cancer Care Associates - Mount Holly
🇺🇸Mount Holly, New Jersey, United States
Azienda Ospedaliera Spedali Civili di Brescia
🇮🇹Brescia, Other, Italy
Azienda Ospedaliera Universitaria Senese
🇮🇹Siena, Other, Italy
Azienda Ospedaliera Citta della Salute e della Scienza di Torino
🇮🇹Torino, Other, Italy
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Institut Catala d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)
🇪🇸Barcelona, Other, Spain
Texas Oncology - Fort Worth 12th Avenue
🇺🇸Fort Worth, Texas, United States
Texas Oncology - Northeast Texas
🇺🇸Tyler, Texas, United States
Oncology and Hematology Assoc of SW VA DBA Blue Ridge Cancer Care
🇺🇸Salem, Virginia, United States
Virginia Cancer Specialists, PC
🇺🇸Fairfax, Virginia, United States
Texas Oncology - Medical City Dallas
🇺🇸Dallas, Texas, United States
Seattle Cancer Care Alliance / University of Washington
🇺🇸Seattle, Washington, United States
Los Angeles Cancer Network / Compassionate Care Research Group
🇺🇸Fountain Valley, California, United States
University of Colorado Health Memorial Hospital
🇺🇸Colorado Springs, Colorado, United States
Poudre Valley Health System (PVHS)
🇺🇸Fort Collins, Colorado, United States
Cancer Centers of Colorado - Denver
🇺🇸Denver, Colorado, United States
SCL Health - St. Mary's Hospital & Medical Center
🇺🇸Grand Junction, Colorado, United States
Miami Cancer Institute at Baptist Health, Inc.
🇺🇸Miami, Florida, United States
Florida Cancer Specialists - North Region
🇺🇸Saint Petersburg, Florida, United States
Cardinal Bernardin Cancer Center / Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Illinois Cancer Specialists
🇺🇸Niles, Illinois, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Karmanos Cancer Institute / Wayne State University
🇺🇸Detroit, Michigan, United States
Illinois Cancer Care
🇺🇸Peoria, Illinois, United States
CareMount Medical Group
🇺🇸Mount Kisco, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Oncology Hematology Care
🇺🇸Cincinnati, Ohio, United States
Royal Adelaide Hospital
🇦🇺Adelaide, Other, Australia
IRCSS Policlinico San Matteo
🇮🇹Pavia, Other, Italy
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Other, Spain
Hospital Clinico Universitario de Salamanca
🇪🇸Salamanca, Other, Spain
Rocky Mountain Cancer Centers - Aurora
🇺🇸Aurora, Colorado, United States
Wake Forest Baptist Medical Center / Wake Forest University
🇺🇸Winston-Salem, North Carolina, United States
Washington University in St Louis
🇺🇸Saint Louis, Missouri, United States
Clinical Research Alliance - Morton Coleman, MD
🇺🇸Westbury, New York, United States
Medical University of South Carolina/Hollings Cancer Center
🇺🇸Charleston, South Carolina, United States