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

NCT ID: NCT01925612

Last Updated: 2018-06-21

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

87 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-08-31

Study Completion Date

2017-05-01

Brief Summary

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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.

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Detailed Description

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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.

Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

brentuximab vedotin

Intervention Type DRUG

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

rituximab

Intervention Type DRUG

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

vincristine

Intervention Type DRUG

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

cyclophosphamide

Intervention Type DRUG

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

prednisone

Intervention Type DRUG

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

doxorubicin

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

brentuximab vedotin

Intervention Type DRUG

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

rituximab

Intervention Type DRUG

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

vincristine

Intervention Type DRUG

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

cyclophosphamide

Intervention Type DRUG

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

prednisone

Intervention Type DRUG

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

doxorubicin

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

brentuximab vedotin

Intervention Type DRUG

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

rituximab

Intervention Type DRUG

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

cyclophosphamide

Intervention Type DRUG

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

prednisone

Intervention Type DRUG

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

doxorubicin

Intervention Type DRUG

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

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.

Group Type ACTIVE_COMPARATOR

rituximab

Intervention Type DRUG

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

vincristine

Intervention Type DRUG

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

cyclophosphamide

Intervention Type DRUG

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

prednisone

Intervention Type DRUG

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

doxorubicin

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

brentuximab vedotin

Intervention Type DRUG

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

rituximab

Intervention Type DRUG

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

cyclophosphamide

Intervention Type DRUG

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

prednisone

Intervention Type DRUG

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

doxorubicin

Intervention Type DRUG

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

Interventions

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brentuximab vedotin

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

Intervention Type DRUG

brentuximab vedotin

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

Intervention Type DRUG

rituximab

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

Intervention Type DRUG

vincristine

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

Intervention Type DRUG

cyclophosphamide

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

Intervention Type DRUG

prednisone

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

Intervention Type DRUG

doxorubicin

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

Intervention Type DRUG

Other Intervention Names

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Adcetris, SGN-35 Adcetris, SGN-35

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Seagen Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Katherine Ruffner

Role: STUDY_DIRECTOR

Seagen Inc.

Locations

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Arizona Oncology Associates, PC - HAL

Phoenix, Arizona, United States

Site Status

Arizona Oncology Associates, PC - HOPE

Tucson, Arizona, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Comprehensive Blood and Cancer Center

Bakersfield, California, United States

Site Status

City of Hope National Medical Center

Duarte, California, United States

Site Status

Sansum Clinic

Santa Barbara, California, United States

Site Status

Stanford Cancer Center

Stanford, California, United States

Site Status

Rocky Mountain Cancer Centers - Aurora

Aurora, Colorado, United States

Site Status

Augusta University

Augusta, Georgia, United States

Site Status

Cardinal Bernardin Cancer Center / Loyola University Medical Center

Maywood, Illinois, United States

Site Status

Illinois Cancer Specialists / Advocate Lutheran General Hospital

Niles, Illinois, United States

Site Status

Norton Cancer Institute

Louisville, Kentucky, United States

Site Status

Johns Hopkins Medical Center

Baltimore, Maryland, United States

Site Status

Henry Ford Health System

Detroit, Michigan, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Billings Clinic Cancer Research

Billings, Montana, United States

Site Status

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Site Status

Summit Medical Group

Morristown, New Jersey, United States

Site Status

Jersey Shore University Medical Center

Neptune City, New Jersey, United States

Site Status

New York Oncology Hematology, P.C.

Albany, New York, United States

Site Status

Mid Ohio Oncology/Hematology Inc

Columbus, Ohio, United States

Site Status

Willamette Valley Cancer Institute and Research Center

Springfield, Oregon, United States

Site Status

Northwest Cancer Specialists, P.C.

Tualatin, Oregon, United States

Site Status

Saint Francis Hospital / Bon Secours

Greenville, South Carolina, United States

Site Status

Tennessee Cancer Specialists

Knoxville, Tennessee, United States

Site Status

Texas Oncology - Austin Midtown

Austin, Texas, United States

Site Status

Texas Oncology - Baylor Sammons Cancer Center

Dallas, Texas, United States

Site Status

US Oncology Investigational Products Center (IPC)

Fort Worth, Texas, United States

Site Status

MD Anderson Cancer Center / University of Texas

Houston, Texas, United States

Site Status

Texas Oncology - San Antonio Medical Center

San Antonio, Texas, United States

Site Status

US Oncology Central Regulatory

The Woodlands, Texas, United States

Site Status

Texas Oncology - Tyler

Tyler, Texas, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Site Status

Virginia Commonwealth University Medical Center

Richmond, Virginia, United States

Site Status

Benaroya Research Institute/Virginia Mason Medical Center

Seattle, Washington, United States

Site Status

Fakultni nemocnice Brno

Brno, , Czechia

Site Status

Fakultni nemocnice Hradec Kralove-oddeleni klinicke hematologie

Hradec Králové, , Czechia

Site Status

Fakultni Nemocnice Kralovske Vinohrady

Prague, , Czechia

Site Status

Fakultni nemocnice v Motole

Prague, , Czechia

Site Status

Centro di Riferimento Oncologico di Aviano

Aviano, , Italy

Site Status

Instituto di Ematologia ed Oncologia Medica

Bologna, , Italy

Site Status

Azienda Ospedaliero-Universitaria Pisana - Ospedale S. Chiara

Pisa, , Italy

Site Status

IRCCS Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, , Italy

Site Status

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

Gdansk, , Poland

Site Status

Malopolskie Centrum Medyczne S.C.

Krakow, , Poland

Site Status

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

Olsztyn, , Poland

Site Status

Hospital de la Santa Creu i Sant Paul

Barcelona, , Spain

Site Status

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Site Status

Institut Català D'oncologia

L'Hospitalet de Llobregat, , Spain

Site Status

Complejo Hospitalano de Navarra Servicio Hematologia

Pamplona, , Spain

Site Status

Countries

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United States Czechia Italy Poland Spain

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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SGN35-017

Identifier Type: -

Identifier Source: org_study_id

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