Combination Chemotherapy and Monoclonal Antibody Therapy in Treating Patients With Non-Hodgkin's Lymphoma

Lymphoma Clinical Trial

Official title:

Phase II Study Of Dose-Adjusted Epoch-Rituximab (EPOCH-R) Chemotherapy For Patients With Previously Untreated Aggressive CD20+ B-Cell Non-Hodgkin's Lymphoma (NHL)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00032019
• Other study ID #: CALGB-50103
• Secondary ID: U10CA031946CALGB
• Status: Completed
• Phase: Phase 2
• First received: March 8, 2002
• Last updated: July 15, 2016
• Start date: February 2002
• Est. completion date: April 2009

Study information

• Verified date: July 2016
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining rituximab with combination chemotherapy may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combining rituximab with combination chemotherapy in treating patients who have previously untreated non-Hodgkin's lymphoma.

Description:

OBJECTIVES:

• Determine the response rate, progression-free survival, and overall survival of patients with previously untreated aggressive CD20+ B-cell diffuse large cell or immunoblastic large cell lymphoma treated with rituximab, doxorubicin, etoposide, vincristine, prednisone, and cyclophosphamide.

• Determine the toxic effects of this regimen in these patients.

• Correlate tumor proliferation rate (MIB-1), bcl-2 expression, and p53 overexpression with complete response rate, progression-free survival, and overall survival in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive rituximab IV on day 1; doxorubicin IV continuously, etoposide IV continuously, and vincristine IV continuously on days 1-4; oral prednisone twice daily on days 1-5; and cyclophosphamide IV on day 5. Patients also receive filgrastim (G-CSF) subcutaneously beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. After 4 courses, patients with complete or partial response receive 2 additional courses.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 25-50 patients will be accrued for this study within 1 year.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 78
• Est. completion date: April 2009
• Est. primary completion date: December 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed stage II, III, or IV diffuse large cell lymphoma and WHO variants

• CD20+ large B-cell lymphoma, including those with immunoblastic features

• CD20+ thymic B-cell lymphoma

• No evidence of indolent lymphoma

• No mantle cell lymphomas or equivocal B-cell lymphomas that express markers of mantle cell lymphoma (e.g., cyclin D) or other subtypes

• No known lymphomatous involvement of the CNS, including the parenchyma or leptomeninges

PATIENT CHARACTERISTICS:

Age:

• Not specified

Performance status:

• CALGB 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,000/mm3*

• Platelet count at least 100,000/mm3* NOTE: * Unless due to lymphoma

Hepatic:

• Bilirubin no greater than 2.0 mg/dL* NOTE: * Unless due to lymphoma or Gilbert's disease

Renal:

• Creatinine no greater than 1.5 mg/dL* NOTE: * Unless due to lymphoma

Cardiovascular:

• LVEF greater than 45%

• No ischemic heart disease

• No myocardial infarction or congestive heart failure within the past year

Other:

• HIV negative

• Not pregnant or nursing

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior cytotoxic chemotherapy

• No other concurrent chemotherapy

Endocrine therapy:

• Prior short-course of glucocorticoids allowed

• No concurrent hormones except for non-disease-related conditions (e.g., insulin for diabetes)

• No concurrent steroids except for adrenal failure

• No concurrent dexamethasone or other steroidal antiemetics

Radiotherapy:

• Prior limited-field radiotherapy allowed

Surgery:

• Not specified

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin

Intervention

Biological:
• filgrastim
Cycle 1: 300 ug (BW < = 70 kg) or 480ug (BW >70 kg) sub Q injection Day 6 until ANC > 5000/uL after nadir counts Subsequent cycle dosages based on previous cycle toxicity or Day 1 Tx toxicity
• rituximab
375 mg/sq m IV infusion Day 1 Cycle 1 Subsequent cycle dosage based on previous cycle or day 1 of tx toxicities

Drug:
• cyclophosphamide
750 mg/sq m IV infusion on Day 5 Cycle 1 Subsequent cycle dosage based on previous cycle or day 1 treatment toxicities
• doxorubicin hydrochloride
10 mg/sq m/day continuous IV infusion on Days 1-4 Cycle 1 Subsequent cycle dosages based on previous cycle and Day 1 treatment toxicities
• etoposide
50 mg/sq m/day continuous IV infusion Days 1-4 Cycle 1 Subsequent cycle dosages based on previous cycle and day 1 of treatment toxicities
• prednisone
60 mg/sq m PO bid days 1-5 of ea cycle
• vincristine sulfate
0.4 mg/sq m/day continuous IV infusion uncapped on Days 1-4 Cycle 1 Subsequent cycle dosages based on previous cycle and day 1 of treatment toxicities

Locations

Country	Name	City	State
Puerto Rico	Puerto Rico Cancer Center at University of Puerto Rico - Medical Sciences Campus	San Juan
United States	Northeast Alabama Regional Medical Center	Anniston	Alabama
United States	Veterans Affairs Medical Center - Asheville	Asheville	North Carolina
United States	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland
United States	Green Mountain Oncology Group	Bennington	Vermont
United States	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland
United States	Hematology Oncology Associates of the Quad Cities	Bettendorf	Iowa
United States	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Veterans Affairs Medical Center - Buffalo	Buffalo	New York
United States	Vermont Cancer Center at University of Vermont	Burlington	Vermont
United States	Cooper University Hospital	Camden	New Jersey
United States	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina
United States	Martha Jefferson Hospital	Charlottesville	Virginia
United States	Louis A. Weiss Memorial Hospital	Chicago	Illinois
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Veterans Affairs Medical Center - Chicago (Westside Hospital)	Chicago	Illinois
United States	Ellis Fischel Cancer Center at University of Missouri - Columbia	Columbia	Missouri
United States	Veterans Affairs Medical Center - Columbia (Truman Memorial)	Columbia	Missouri
United States	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio
United States	NorthEast Oncology Associates	Concord	North Carolina
United States	Veterans Affairs Medical Center - Dallas	Dallas	Texas
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Veterans Affairs Medical Center - Durham	Durham	North Carolina
United States	CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.	East Syracuse	New York
United States	Elmhurst Hospital Center	Elmhurst	New York
United States	Cape Fear Valley Health System	Fayetteville	North Carolina
United States	Broward General Medical Center	Fort Lauderdale	Florida
United States	Fort Wayne Medical Oncology and Hematology, Incorporated	Fort Wayne	Indiana
United States	Memorial Regional Hospital Comprehensive Cancer Center	Hollywood	Florida
United States	New Hampshire Oncology-Hematology, PA - Hooksett	Hooksett	New Hampshire
United States	St. Mary's Medical Center	Huntington	West Virginia
United States	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa
United States	Queens Cancer Center of Queens Hospital	Jamaica	New York
United States	CCOP - Kansas City	Kansas City	Missouri
United States	Lenoir Memorial Hospital Cancer Center	Kinston	North Carolina
United States	Rebecca and John Moores UCSD Cancer Center	La Jolla	California
United States	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	Veterans Affairs Medical Center - Las Vegas	Las Vegas	Nevada
United States	Norris Cotton Cancer Center at Dartmouth Medical School	Lebanon	New Hampshire
United States	Cedars-Sinai Comprehensive Cancer Center at Cedars-Sinai Medical Center	Los Angeles	California
United States	Baptist Hospital East - Louisville	Louisville	Kentucky
United States	CCOP - North Shore University Hospital	Manhasset	New York
United States	North Shore University Hospital	Manhasset	New York
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota
United States	Veterans Affairs Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Mount Sinai Medical Center, NY	New York	New York
United States	New York Weill Cornell Cancer Center at Cornell University	New York	New York
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Virginia Oncology Associates - Norfolk	Norfolk	Virginia
United States	Oklahoma University Medical Center at University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	UNMC Eppley Cancer Center at the University of Nebraska Medical Center	Omaha	Nebraska
United States	Florida Hospital Cancer Institute	Orlando	Florida
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	FirstHealth Moore Regional Hospital	Pinehurst	North Carolina
United States	Western Pennsylvania Hospital	Pittsburgh	Pennsylvania
United States	Lifespan: The Miriam Hospital	Providence	Rhode Island
United States	MBCCOP - Massey Cancer Center	Richmond	Virginia
United States	West Suburban Center for Cancer Care	River Forest	Illinois
United States	Oncology and Hematology Associates of Southwest Virginia, Inc.	Roanoke	Virginia
United States	Saint Anthony Medical Center	Rockford	Illinois
United States	Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph	Saint Joseph	Michigan
United States	Missouri Baptist Cancer Center	Saint Louis	Missouri
United States	Naval Medical Center - San Diego	San Diego	California
United States	Veterans Affairs Medical Center - San Diego	San Diego	California
United States	UCSF Comprehensive Cancer Center	San Francisco	California
United States	Veterans Affairs Medical Center - San Francisco	San Francisco	California
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	Barnes-Jewish Hospital	St. Louis	Missouri
United States	University Hospital at State University of New York - Upstate Medical University	Syracuse	New York
United States	Veterans Affairs Medical Center - Syracuse	Syracuse	New York
United States	Lombardi Cancer Center at Georgetown University Medical Center	Washington	District of Columbia
United States	Veterans Affairs Medical Center - Washington, DC	Washington	District of Columbia
United States	Walter Reed Army Medical Center	Washington	District of Columbia
United States	Palm Beach Cancer Institute	West Palm Beach	Florida
United States	New Hanover Regional Medical Center	Wilmington	North Carolina
United States	CCOP - Southeast Cancer Control Consortium	Winston-Salem	North Carolina
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina
United States	University of Massachusetts Memorial Medical Center - University Campus	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (2)

Hsi ED, Said J, Johnson JL, et al.: Biologic prognostic markers in diffuse large B-cell lymphoma patients treated with dose adjusted EPOCH-R: a CALGB 50103 correlative science study. [Abstract] Blood 112 (11): A-476, 2008.

Wilson WH, Porcu P, Hurd D, et al.: Phase II study of dose-adjusted EPOCH-R in untreated de novo CD20+ diffuse large B-cell lymphoma (DLBCL)-CALGB 50103. [Abstract] J Clin Oncol 23 (Suppl 16): A-6530, 567s, 2005.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response		5 months	No
Secondary	Progression free Survival		Study entry to progression or tx related death	No
Secondary	Overall survival		Study entry to death from any cause	No
Secondary	Toxicity		q 2cycles on Tx, then q 6 mon for 2 yrs, then at relapse	Yes