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

NCT01925612 | Terminated Phase 2 Results

• 1 other identifier: SGN35-017
• Study Type: interventional
• Target: 87
• Locations: 5 countries
• Sites: 51

Brief Summary

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.

Conditions

Lymphoma, B-cell; Lymphoma, Large B-cell, Diffuse

Keywords

Antibodies, Monoclonal; Antibody-Drug Conjugate; Antigens, CD30; Drug Therapy; Hematologic Diseases; Lymphoma, B-cell; Lymphoma, Large B-cell, Diffuse; Monomethyl auristatin E

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (3)

• Objective Response Rate

  Up to 6 months

• Progression-free Survival

  Up to approximately 4 years

• Overall Survival

  Up to approximately 4 years

Study Arms (5)

Part 1: BV(1.2 mg/kg) + RCHOP

EXPERIMENTAL

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: brentuximab vedotin; Drug: rituximab; Drug: vincristine; Drug: cyclophosphamide; Drug: prednisone; Drug: doxorubicin

Part 1: BV(1.8 mg/kg) + RCHOP

EXPERIMENTAL

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: brentuximab vedotin; Drug: rituximab; Drug: vincristine; Drug: cyclophosphamide; Drug: prednisone; Drug: doxorubicin

Part 2: BV(1.8 mg/kg) + RCHP

EXPERIMENTAL

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: brentuximab vedotin; Drug: rituximab; Drug: cyclophosphamide; Drug: prednisone; Drug: doxorubicin

Part 3: RCHOP

ACTIVE COMPARATOR

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; Drug: vincristine; Drug: cyclophosphamide; Drug: prednisone; Drug: doxorubicin

Part 3: BV(1.8 mg/kg) + RCHP

EXPERIMENTAL

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: brentuximab vedotin; Drug: rituximab; Drug: cyclophosphamide; Drug: prednisone; Drug: doxorubicin

Interventions

brentuximab vedotin DRUG

1.2 mg/kg by IV infusion every 3 weeks for up to 6 cycles

Also known as: Adcetris, SGN-35

Part 1: BV(1.2 mg/kg) + RCHOP

rituximab DRUG

375 mg/m2 every 3 weeks by IV infusion for up to 6 cycles

Part 1: BV(1.2 mg/kg) + RCHOP; Part 1: BV(1.8 mg/kg) + RCHOP; Part 2: BV(1.8 mg/kg) + RCHP; Part 3: BV(1.8 mg/kg) + RCHP; Part 3: RCHOP

vincristine DRUG

1.4 mg/m2 every 3 weeks by IV infusion for up to 6 cycles (dose capped at 2 mg total)

Part 1: BV(1.2 mg/kg) + RCHOP; Part 1: BV(1.8 mg/kg) + RCHOP; Part 3: RCHOP

cyclophosphamide DRUG

750 mg/m2 every 3 weeks by IV infusion for up to 6 cycles

Part 1: BV(1.2 mg/kg) + RCHOP; Part 1: BV(1.8 mg/kg) + RCHOP; Part 2: BV(1.8 mg/kg) + RCHP; Part 3: BV(1.8 mg/kg) + RCHP; Part 3: RCHOP

prednisone DRUG

100 mg on Days 1 to 5 of each 3-week cycle, orally for up to 6 cycles

Part 1: BV(1.2 mg/kg) + RCHOP; Part 1: BV(1.8 mg/kg) + RCHOP; Part 2: BV(1.8 mg/kg) + RCHP; Part 3: BV(1.8 mg/kg) + RCHP; Part 3: RCHOP

doxorubicin DRUG

50 mg/m2 every 3 weeks by IV infusion for up to 6 cycles

Part 1: BV(1.2 mg/kg) + RCHOP; Part 1: BV(1.8 mg/kg) + RCHOP; Part 2: BV(1.8 mg/kg) + RCHP; Part 3: BV(1.8 mg/kg) + RCHP; Part 3: RCHOP

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Seagen Inc.: lead

Study Sites (51)

Arizona Oncology Associates, PC - HAL

Phoenix, Arizona, 85016, United States

Location

Arizona Oncology Associates, PC - HOPE

Tucson, Arizona, 85710, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Comprehensive Blood and Cancer Center

Bakersfield, California, 93309, United States

Location

City of Hope National Medical Center

Duarte, California, 91010-3000, United States

Location

Sansum Clinic

Santa Barbara, California, 93105, United States

Location

Stanford Cancer Center

Stanford, California, 94305, United States

Location

Rocky Mountain Cancer Centers - Aurora

Aurora, Colorado, 80012, United States

Location

Augusta University

Augusta, Georgia, 30912, United States

Location

Cardinal Bernardin Cancer Center / Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Illinois Cancer Specialists / Advocate Lutheran General Hospital

Niles, Illinois, 60714, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40202, United States

Location

Johns Hopkins Medical Center

Baltimore, Maryland, 21231, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Billings Clinic Cancer Research

Billings, Montana, 59101, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

Summit Medical Group

Morristown, New Jersey, 07962, United States

Location

Jersey Shore University Medical Center

Neptune City, New Jersey, 07754, United States

Location

New York Oncology Hematology, P.C.

Albany, New York, 12206, United States

Location

Mid Ohio Oncology/Hematology Inc

Columbus, Ohio, 43219, United States

Location

Willamette Valley Cancer Institute and Research Center

Springfield, Oregon, 97477, United States

Location

Northwest Cancer Specialists, P.C.

Tualatin, Oregon, 97062, United States

Location

Saint Francis Hospital / Bon Secours

Greenville, South Carolina, 29601, United States

Location

Tennessee Cancer Specialists

Knoxville, Tennessee, 37909, United States

Location

Texas Oncology - Austin Midtown

Austin, Texas, 78705, United States

Location

Texas Oncology - Baylor Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

US Oncology Investigational Products Center (IPC)

Fort Worth, Texas, 76177, 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, 78229, United States

Location

US Oncology Central Regulatory

The Woodlands, Texas, 77380, United States

Location

Texas Oncology - Tyler

Tyler, Texas, 75702, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Virginia Commonwealth University Medical Center

Richmond, Virginia, 23298, United States

Location

Benaroya Research Institute/Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

Fakultni nemocnice Brno

Brno, 625 00, Czechia

Location

Fakultni nemocnice Hradec Kralove-oddeleni klinicke hematologie

Hradec Králové, 500 05, Czechia

Location

Fakultni Nemocnice Kralovske Vinohrady

Prague, 100 34, Czechia

Location

Fakultni nemocnice v Motole

Prague, 150 06, Czechia

Location

Centro di Riferimento Oncologico di Aviano

Aviano, 33081, Italy

Location

Instituto di Ematologia ed Oncologia Medica

Bologna, 40138, Italy

Location

Azienda Ospedaliero-Universitaria Pisana - Ospedale S. Chiara

Pisa, 56126, Italy

Location

IRCCS Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, 71013, Italy

Location

COPERNICUS Podmiot Leczniczy Sp. z o.o. Wojewodzkie Centrum Onkologii

Gdansk, 80-219, Poland

Location

Malopolskie Centrum Medyczne S.C.

Krakow, 30-510, Poland

Location

Samodzielny Publiczny Zaklad Opieki Zdrowotnej Ministerstwa Spraw Wewnetrznych z Warminsko-Mazurskim

Olsztyn, 10-228, Poland

Location

Hospital de la Santa Creu i Sant Paul

Barcelona, 08025, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Institut Català D'oncologia

L'Hospitalet de Llobregat, 08907, Spain

Location

Complejo Hospitalano de Navarra Servicio Hematologia

Pamplona, 31130, Spain

Location

MeSH Terms

Conditions

Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Hematologic Diseases

Interventions

Brentuximab Vedotin; Rituximab; Vincristine; Cyclophosphamide; Prednisone; Doxorubicin

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; 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; Antibodies, Monoclonal, Murine-Derived; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Aminoglycosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Seattle Genetics, Inc.

medinfo@seagen.com

(855)473-2436

Study Officials

• Katherine Ruffner

  Seagen Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: August 15, 2013
• First Posted: August 20, 2013
• Study Start: August 1, 2013
• Primary Completion: May 1, 2017
• Study Completion: May 1, 2017
• Last Updated: June 21, 2018
• Results First Posted: June 21, 2018

Record last verified: 2018-05

Locations

IT (4); CZ (4); PL (3); US (36); ES (4)