Study of Brentuximab Vedotin Combined With RCHOP or RCHP in Front-line Treatment of Patients With Diffuse Large B-cell Lymphoma (DLBCL)

A Phase 2 Study of Brentuximab Vedotin in Combination With Standard of Care Treatment (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone [RCHOP]) or RCHP (Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone) as Front-line Therapy in Patients With Diffuse Large B-cell Lymphoma (DLBCL)

This study has 3 parts. The purpose of Part 1 of this study is to assess the safety and efficacy of brentuximab vedotin in combination with RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) (known as BV+RCHOP) in patients with DLBCL who have never been treated. Patients will be randomly assigned in a 1:1 ratio to receive RCHOP together with 1 of 2 doses of brentuximab vedotin. Patients will be tested to see if there is a difference in side effects between the 2 groups.

The purpose of Part 2 of this study is to assess the safety and efficacy of brentuximab vedotin in combination with RCHP (rituximab, cyclophosphamide, doxorubicin, and prednisone) (known as BV+RCHP) in patients with CD30-positive DLBCL who have never been treated. Patients will be enrolled to receive RCHP together with 1.8mg/kg of brentuximab vedotin.

The purpose of Part 3 of this study is to assess the safety and efficacy of BV+RCHP compared to standard RCHOP in patients with CD30-positive DLBCL that have never been treated. Patients will be randomly assigned in a 1:1 ratio to receive either BV+RCHP or RCHOP. Patients will be tested to see if there is a difference in side effects between the 2 groups.

Study Overview

• Status: Terminated
• Conditions: Lymphoma, Large B-cell, Diffuse; Lymphoma, B-cell
• Intervention / Treatment: Drug: rituximab; Drug: cyclophosphamide; Drug: doxorubicin; Drug: vincristine; Drug: prednisone; Drug: brentuximab vedotin; Drug: brentuximab vedotin

Detailed Description

In the first part of this study, patients in the 2 groups were tested to see if there was a difference in the response to treatment and whether there were differences in the side effects (unwanted effects).

The second and third parts of the study are being done to see if there are any side effects (unwanted effects) of the higher dose of brentuximab vedotin when combined with a modified version of RCHOP that omits vincristine. The third part of the study is being done to see if there is a difference between BV+RCHP and RCHOP in the response to treatment.

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czechia
  • Brno, Czechia, 625 00
    • Fakultní nemocnice Brno
  • Hradec Kralove, Czechia, 500 05
    • Fakultni nemocnice Hradec Kralove-oddeleni klinicke hematologie
  • Praha 10, Czechia, 100 34
    • Fakultni nemocnice Kralovske Vinohrady
  • Praha 5, Czechia, 150 06
    • Fakultni nemocnice v Motole
• Italy
  • Aviano, Italy, 33081
    • Centro di Riferimento Oncologico di Aviano
  • Bologna, Italy, 40138
    • Instituto di Ematologia ed Oncologia Medica
  • Pisa, Italy, 56126
    • Azienda Ospedaliero-Universitaria Pisana - Ospedale S. Chiara
  • San Giovanni Rotondo, Italy, 71013
    • IRCCS Ospedale Casa Sollievo della Sofferenza
• Poland
  • Gdansk, Poland, 80-219
    • COPERNICUS Podmiot Leczniczy Sp. z o.o. Wojewodzkie Centrum Onkologii
  • Krakow, Poland, 30-510
    • Malopolskie Centrum Medyczne s.c.
  • Olsztyn, Poland, 10-228
    • Samodzielny Publiczny Zaklad Opieki Zdrowotnej Ministerstwa Spraw Wewnetrznych z Warminsko-Mazurskim
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu i Sant Paul
  • L'Hospitalet de Llobregat, Spain, 08907
    • Institut Catala d'Oncologia
  • Pamplona, Spain, 31130
    • Complejo Hospitalano de Navarra Servicio Hematologia
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Arizona Oncology Associates, PC - HAL
    • Tucson, Arizona, United States, 85710
      • Arizona Oncology Associates, PC - HOPE
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Bakersfield, California, United States, 93309
      • Comprehensive Blood and Cancer Center
    • Duarte, California, United States, 91010-3000
      • City of Hope National Medical Center
    • Santa Barbara, California, United States, 93105
      • Sansum Clinic
    • Stanford, California, United States, 94305
      • Stanford Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Rocky Mountain Cancer Centers - Aurora
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta University
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Cardinal Bernardin Cancer Center / Loyola University Medical Center
    • Niles, Illinois, United States, 60714
      • Illinois Cancer Specialists / Advocate Lutheran General Hospital
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Cancer Institute
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic Cancer Research
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Centers of Nevada
  • New Jersey
    • Morristown, New Jersey, United States, 07962
      • Summit Medical Group
    • Neptune, New Jersey, United States, 07754
      • Jersey Shore University Medical Center
  • New York
    • Albany, New York, United States, 12206
      • New York Oncology Hematology, P.C.
  • Ohio
    • Columbus, Ohio, United States, 43219
      • Mid Ohio Oncology/Hematology Inc
  • Oregon
    • Springfield, Oregon, United States, 97477
      • Willamette Valley Cancer Institute and Research Center
    • Tualatin, Oregon, United States, 97062
      • Northwest Cancer Specialists, P.C.
  • South Carolina
    • Greenville, South Carolina, United States, 29601
      • Saint Francis Hospital / Bon Secours
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • Tennessee Cancer Specialists
  • Texas
    • Austin, Texas, United States, 78705
      • Texas Oncology - Austin Midtown
    • Dallas, Texas, United States, 75246
      • Texas Oncology - Baylor Sammons Cancer Center
    • Fort Worth, Texas, United States, 76177
      • US Oncology Investigational Products Center (IPC)
    • Houston, Texas, United States, 77030-4095
      • MD Anderson Cancer Center / University of Texas
    • San Antonio, Texas, United States, 78229
      • Texas Oncology - San Antonio Medical Center
    • The Woodlands, Texas, United States, 77380
      • US Oncology Central Regulatory
    • Tyler, Texas, United States, 75702
      • Texas Oncology - Tyler
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists, PC
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University Medical Center
  • Washington
    • Seattle, Washington, United States, 98101
      • Benaroya Research Institute/Virginia Mason Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Treatment-naive patients with systemic de novo or transformed diffuse large B cell lymphoma (DLBCL) or follicular non-Hodgkin lymphoma (NHL) grade 3b
• International Prognostic Index (IPI) score greater than or equal to 3 for patients greater than 60 years of age or age-adjusted IPI (aaIPI) score of 2 or 3 for patients less than or equal to 60 years of age
• Stage IAX (bulk defined as single lymph node mass >10 cm in diameter), IB-IV disease
• Measurable disease of at least 1.5 cm
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2
• Patients in Parts 2 and 3 must have histologically confirmed diagnosis of CD30-positive DLBCL

Exclusion Criteria:

• Previous history of treated indolent lymphoma
• History of another primary malignancy that has not been in remission for 3 years

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: BV(1.2 mg/kg) + RCHOP; Brentuximab vedotin 1.2 mg/kg plus rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone Part 1 of the study is a phase 2, randomized, open-label, multicenter study designed to evaluate the antitumor activity and safety of brentuximab vedotin when administered in combination with standard RCHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Patients in this arm were randomized into the 1.2 mg/kg brentuximab vedotin dosing cohort, to be administered in combination with RCHOP.	Drug: rituximab; 375 mg/m2 every 3 weeks by IV infusion for up to 6 cycles; Drug: cyclophosphamide; 750 mg/m2 every 3 weeks by IV infusion for up to 6 cycles; Drug: doxorubicin; 50 mg/m2 every 3 weeks by IV infusion for up to 6 cycles; Drug: vincristine; 1.4 mg/m2 every 3 weeks by IV infusion for up to 6 cycles (dose capped at 2 mg total); Drug: prednisone; 100 mg on Days 1 to 5 of each 3-week cycle, orally for up to 6 cycles; Drug: brentuximab vedotin; 1.2 mg/kg by IV infusion every 3 weeks for up to 6 cycles; Other Names: Adcetris, SGN-35; Drug: brentuximab vedotin; 1.8 mg/kg by IV infusion every 3 weeks for up to 6 cycles; Other Names: Adcetris, SGN-35
Experimental: Part 1: BV(1.8 mg/kg) + RCHOP; Brentuximab vedotin 1.8 mg/kg plus rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone Part 1 of the study is a phase 2, randomized, open-label, multicenter study designed to evaluate the antitumor activity and safety of brentuximab vedotin when administered in combination with standard RCHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Patients in this arm were randomized into the 1.8 mg/kg brentuximab vedotin dosing cohort, to be administered in combination with RCHOP.	Drug: rituximab; 375 mg/m2 every 3 weeks by IV infusion for up to 6 cycles; Drug: cyclophosphamide; 750 mg/m2 every 3 weeks by IV infusion for up to 6 cycles; Drug: doxorubicin; 50 mg/m2 every 3 weeks by IV infusion for up to 6 cycles; Drug: vincristine; 1.4 mg/m2 every 3 weeks by IV infusion for up to 6 cycles (dose capped at 2 mg total); Drug: prednisone; 100 mg on Days 1 to 5 of each 3-week cycle, orally for up to 6 cycles; Drug: brentuximab vedotin; 1.2 mg/kg by IV infusion every 3 weeks for up to 6 cycles; Other Names: Adcetris, SGN-35; Drug: brentuximab vedotin; 1.8 mg/kg by IV infusion every 3 weeks for up to 6 cycles; Other Names: Adcetris, SGN-35
Experimental: Part 2: BV(1.8 mg/kg) + RCHP; Brentuximab vedotin 1.8 mg/kg plus rituximab, cyclophosphamide, doxorubicin, prednisone Part 2 of the study is a phase 2, non-randomized, open-label, multicenter study designed to evaluate the antitumor activity and safety of brentuximab vedotin 1.8 mg/kg when administered in combination with RCHP chemotherapy (rituximab, cyclophosphamide, doxorubicin, and prednisone). Patients in this treatment arm were enrolled into a dosing cohort with 1.8 mg/kg brentuximab vedotin administered in combination with RCHP.	Drug: rituximab; 375 mg/m2 every 3 weeks by IV infusion for up to 6 cycles; Drug: cyclophosphamide; 750 mg/m2 every 3 weeks by IV infusion for up to 6 cycles; Drug: doxorubicin; 50 mg/m2 every 3 weeks by IV infusion for up to 6 cycles; Drug: prednisone; 100 mg on Days 1 to 5 of each 3-week cycle, orally for up to 6 cycles; Drug: brentuximab vedotin; 1.2 mg/kg by IV infusion every 3 weeks for up to 6 cycles; Other Names: Adcetris, SGN-35; Drug: brentuximab vedotin; 1.8 mg/kg by IV infusion every 3 weeks for up to 6 cycles; Other Names: Adcetris, SGN-35
Active Comparator: Part 3: RCHOP; Rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone Part 3 of the study is a phase 2, randomized, open-label, multicenter study designed to evaluate the antitumor activity and safety of brentuximab vedotin 1.8 mg/kg when administered in combination with RCHP chemotherapy compared to RCHOP chemotherapy alone. Patients in this treatment arm were randomized to receive RCHOP treatment alone.	Drug: rituximab; 375 mg/m2 every 3 weeks by IV infusion for up to 6 cycles; Drug: cyclophosphamide; 750 mg/m2 every 3 weeks by IV infusion for up to 6 cycles; Drug: doxorubicin; 50 mg/m2 every 3 weeks by IV infusion for up to 6 cycles; Drug: vincristine; 1.4 mg/m2 every 3 weeks by IV infusion for up to 6 cycles (dose capped at 2 mg total); Drug: prednisone; 100 mg on Days 1 to 5 of each 3-week cycle, orally for up to 6 cycles
Experimental: Part 3: BV(1.8 mg/kg) + RCHP; Brentuximab vedotin 1.8 mg/kg plus rituximab, cyclophosphamide, doxorubicin, prednisone Part 3 of the study is a phase 2, randomized, open-label, multicenter study designed to evaluate the antitumor activity and safety of brentuximab vedotin 1.8 mg/kg when administered in combination with RCHP chemotherapy compared to RCHOP chemotherapy alone. Patients in this treatment arm were randomized to receive RCHOP treatment alone. Randomization in this part of the study is for the purpose of evaluating the safety of 1.8 mg/kg brentuximab vedotin in combination with RCHP versus standard RCHOP chemotherapy. Part 3 of the study is a phase 2, randomized, open-label, multicenter study designed to evaluate the antitumor activity and safety of brentuximab vedotin 1.8 mg/kg when administered in combination with RCHP chemotherapy compared to RCHOP chemotherapy alone. Patients in this treatment arm were randomized to receive 1.8 mg/kg brentuximab vedotin administered in combination with RCHP.	Drug: rituximab; 375 mg/m2 every 3 weeks by IV infusion for up to 6 cycles; Drug: cyclophosphamide; 750 mg/m2 every 3 weeks by IV infusion for up to 6 cycles; Drug: doxorubicin; 50 mg/m2 every 3 weeks by IV infusion for up to 6 cycles; Drug: prednisone; 100 mg on Days 1 to 5 of each 3-week cycle, orally for up to 6 cycles; Drug: brentuximab vedotin; 1.2 mg/kg by IV infusion every 3 weeks for up to 6 cycles; Other Names: Adcetris, SGN-35; Drug: brentuximab vedotin; 1.8 mg/kg by IV infusion every 3 weeks for up to 6 cycles; Other Names: Adcetris, SGN-35

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Remission Rate	Number (count) of participants that achieved remission according to the Revised Response Criteria for Malignant Lymphoma (Cheson 2007).	Up to 6 months
Incidence of Adverse Events	Number (count) of participants that experienced at least 1 adverse event.	Up to 6 months
Incidence of Laboratory Abnormalities	Number (count) of participants that experienced a Grade 3 or higher maximum post-baseline laboratory toxicity (hematology and chemistry). Grades are defined using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), v4.03. Grade 1 = mild, no intervention needed; Grade 2 = moderate, minimal intervention needed; Grade 3 = severe or medically significant, hospitalization is required; Grade 4 = life-threatening, urgent intervention needed; Grade 5 = death related to adverse event.	Up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	Number (count) of participants that achieved complete or partial remission at the end of treatment according to the Revised Response Criteria for Malignant Lymphoma (Cheson 2007)	Up to 6 months
Progression-free Survival	Median progression-free survival (in months) and observed minimum-maximum range.	Up to approximately 4 years
Overall Survival	Median overall survival (in months) and observed minimum-maximum range.	Up to approximately 4 years

Collaborators and Investigators

• Sponsor: Seagen Inc.
• Investigators: Study Director: Katherine Ruffner, Seagen Inc.

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): May 1, 2017
• Study Completion (Actual): May 1, 2017

Study Registration Dates

• First Submitted: August 15, 2013
• First Submitted That Met QC Criteria: August 15, 2013
• First Posted (Estimate): August 20, 2013

Study Record Updates

• Last Update Posted (Actual): June 21, 2018
• Last Update Submitted That Met QC Criteria: May 22, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Drug Therapy; Hematologic Diseases; Antibody-Drug Conjugate; Antibodies, Monoclonal; Antigens, CD30; Monomethyl auristatin E; Lymphoma, B-cell; Lymphoma, Large B-cell, Diffuse
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Cyclophosphamide; Rituximab; Prednisone; Doxorubicin; Antibodies, Monoclonal; Vincristine; Brentuximab Vedotin
• Other Study ID Numbers: SGN35-017