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

Lymphoma, B-cell Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01925612
• Other study ID #: SGN35-017
• Status: Terminated
• Phase: Phase 2
• Start date: August 2013
• Est. completion date: May 1, 2017

Study information

• Verified date: May 2018
• Source: Seattle Genetics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 87
• Est. completion date: May 1, 2017
• Est. primary completion date: May 1, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-cell, Diffuse

Intervention

Drug:
• brentuximab vedotin
1.2 mg/kg by IV infusion every 3 weeks for up to 6 cycles
• brentuximab vedotin
1.8 mg/kg by IV infusion every 3 weeks for up to 6 cycles
• rituximab
375 mg/m2 every 3 weeks by IV infusion for up to 6 cycles
• vincristine
1.4 mg/m2 every 3 weeks by IV infusion for up to 6 cycles (dose capped at 2 mg total)
• cyclophosphamide
750 mg/m2 every 3 weeks by IV infusion for up to 6 cycles
• prednisone
100 mg on Days 1 to 5 of each 3-week cycle, orally for up to 6 cycles
• doxorubicin
50 mg/m2 every 3 weeks by IV infusion for up to 6 cycles

Locations

Country	Name	City	State
Czechia	Fakultni nemocnice Brno	Brno
Czechia	Fakultni nemocnice Hradec Kralove-oddeleni klinicke hematologie	Hradec Kralove
Czechia	Fakultni Nemocnice Kralovske Vinohrady	Praha 10
Czechia	Fakultni nemocnice v Motole	Praha 5
Italy	Centro di Riferimento Oncologico di Aviano	Aviano
Italy	Instituto di Ematologia ed Oncologia Medica	Bologna
Italy	Azienda Ospedaliero-Universitaria Pisana - Ospedale S. Chiara	Pisa
Italy	IRCCS Ospedale Casa Sollievo della Sofferenza	San Giovanni Rotondo
Poland	COPERNICUS Podmiot Leczniczy Sp. z o.o. Wojewodzkie Centrum Onkologii	Gdansk
Poland	Malopolskie Centrum Medyczne S.C.	Krakow
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnej Ministerstwa Spraw Wewnetrznych z Warminsko-Mazurskim	Olsztyn
Spain	Hospital de la Santa Creu i Sant Paul	Barcelona
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Institut Català D'oncologia	L'Hospitalet de Llobregat
Spain	Complejo Hospitalano de Navarra Servicio Hematologia	Pamplona
United States	New York Oncology Hematology, P.C.	Albany	New York
United States	Augusta University	Augusta	Georgia
United States	Rocky Mountain Cancer Centers - Aurora	Aurora	Colorado
United States	Texas Oncology - Austin Midtown	Austin	Texas
United States	Comprehensive Blood and Cancer Center	Bakersfield	California
United States	Johns Hopkins Medical Center	Baltimore	Maryland
United States	Billings Clinic Cancer Research	Billings	Montana
United States	Mid Ohio Oncology/Hematology Inc	Columbus	Ohio
United States	Texas Oncology - Baylor Sammons Cancer Center	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	City of Hope National Medical Center	Duarte	California
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	US Oncology Investigational Products Center (IPC)	Fort Worth	Texas
United States	Saint Francis Hospital / Bon Secours	Greenville	South Carolina
United States	MD Anderson Cancer Center / University of Texas	Houston	Texas
United States	Tennessee Cancer Specialists	Knoxville	Tennessee
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Cardinal Bernardin Cancer Center / Loyola University Medical Center	Maywood	Illinois
United States	Summit Medical Group	Morristown	New Jersey
United States	Jersey Shore University Medical Center	Neptune	New Jersey
United States	Illinois Cancer Specialists / Advocate Lutheran General Hospital	Niles	Illinois
United States	Arizona Oncology Associates, PC - HAL	Phoenix	Arizona
United States	Virginia Commonwealth University Medical Center	Richmond	Virginia
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	Texas Oncology - San Antonio Medical Center	San Antonio	Texas
United States	Sansum Clinic	Santa Barbara	California
United States	Benaroya Research Institute/Virginia Mason Medical Center	Seattle	Washington
United States	Willamette Valley Cancer Institute and Research Center	Springfield	Oregon
United States	Stanford Cancer Center	Stanford	California
United States	US Oncology Central Regulatory	The Woodlands	Texas
United States	Northwest Cancer Specialists, P.C.	Tualatin	Oregon
United States	Arizona Oncology Associates, PC - HOPE	Tucson	Arizona
United States	Texas Oncology - Tyler	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Seattle Genetics, Inc.

Countries where clinical trial is conducted

United States,  Czechia,  Italy,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Incidence of Adverse Events	Number (count) of participants that experienced at least 1 adverse event.	Up to 6 months
Primary	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	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
Secondary	Progression-free Survival	Median progression-free survival (in months) and observed minimum-maximum range.	Up to approximately 4 years
Secondary	Overall Survival	Median overall survival (in months) and observed minimum-maximum range.	Up to approximately 4 years