S0019 Combination Chemotherapy With or Without Rituximab in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

A Randomized Phase III Trial of ICE Chemotherapy With or Without Rituximab for the Treatment of Relapsed or Refractory CD20 Expressing Aggressive B-Cell Non-Hodgkin's Lymphomas in Patients Not Suitable for High Dose Therapy and PBSCT

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 cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. It is not yet known whether combination chemotherapy is more effective with or without rituximab for non-Hodgkin's lymphoma.

PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without rituximab in treating patients who have relapsed or refractory non-Hodgkin's lymphoma.

Study Overview

• Status: Terminated
• Conditions: Lymphoma
• Intervention / Treatment: Drug: carboplatin; Drug: etoposide; Biological: rituximab; Drug: ifosfamide; Biological: filgrastim

Detailed Description

OBJECTIVES: I. Compare the progression-free and overall survival of patients with relapsed or refractory, CD20 expressing, aggressive, B-cell non-Hodgkin's lymphoma treated with ifosfamide, carboplatin, and etoposide with or without rituximab. II. Compare the unconfirmed response rate of patients treated with these regimens. III. Determine the toxicity of ifosfamide, carboplatin, and etoposide with rituximab in these patients.

OUTLINE: This is a randomized study. Patients are stratified according to histology (large B-cell vs other) and risk group (low/low-intermediate vs high-intermediate/high). Patients are randomized to one of two treatment arms. Arm I: Patients receive etoposide IV over 1 hour on days 1-3, carboplatin IV over 1 hour on day 2, ifosfamide IV continuously for 24 hours on day 2, and filgrastim (G-CSF) subcutaneously (SC) on days 5-12. Treatment continues every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive rituximab IV on day 1, etoposide IV over 1 hour on days 2-4, carboplatin IV over 1 hour on day 3, ifosfamide IV continuously for 24 hours on day 3, and G-CSF SC on days 6-13. Patients also receive rituximab IV on day 8 of course 1. Treatment continues every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually for 5 years.

PROJECTED ACCRUAL: A total of 376 patients (188 per arm) will be accrued for this study within 3 years.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36688
      • MBCCOP - Gulf Coast
  • Arizona
    • Phoenix, Arizona, United States, 85006-2726
      • CCOP - Greater Phoenix
    • Phoenix, Arizona, United States, 85012
      • Veterans Affairs Medical Center - Phoenix (Hayden)
    • Tucson, Arizona, United States, 85724
      • Arizona Cancer Center
    • Tucson, Arizona, United States, 85723
      • Veterans Affairs Medical Center - Tucson
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
    • Little Rock, Arkansas, United States, 72205
      • Veterans Affairs Medical Center - Little Rock (McClellan)
  • California
    • Duarte, California, United States, 91010-3000
      • Cancer Center and Beckman Research Institute, City of Hope
    • Long Beach, California, United States, 90822
      • Veterans Affairs Medical Center - Long Beach
    • Los Angeles, California, United States, 90095-1781
      • Jonsson Comprehensive Cancer Center, UCLA
    • Los Angeles, California, United States, 90033-0804
      • USC/Norris Comprehensive Cancer Center and Hospital
    • Martinez, California, United States, 94553
      • Veterans Affairs Outpatient Clinic - Martinez
    • Oakland, California, United States, 94609-3305
      • CCOP - Bay Area Tumor Institute
    • Orange, California, United States, 92868
      • Chao Family Comprehensive Cancer Center
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center
    • Santa Rosa, California, United States, 95403
      • CCOP - Santa Rosa Memorial Hospital
    • Travis Air Force Base, California, United States, 94535
      • David Grant Medical Center
  • Colorado
    • Denver, Colorado, United States, 80220
      • Veterans Affairs Medical Center - Denver
    • Denver, Colorado, United States, 80010
      • University of Colorado Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30342-1701
      • CCOP - Atlanta Regional
    • Fort Gordon, Georgia, United States, 30905-5650
      • Dwight David Eisenhower Army Medical Center
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Cancer Research Center of Hawaii
  • Illinois
    • Decatur, Illinois, United States, 62526
      • CCOP - Central Illinois
    • Hines, Illinois, United States, 60141
      • Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital)
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Kansas
    • Kansas City, Kansas, United States, 66160-7357
      • University of Kansas Medical Center
    • Wichita, Kansas, United States, 67214-3882
      • CCOP - Wichita
    • Wichita, Kansas, United States, 67218
      • Veterans Affairs Medical Center - Wichita
  • Kentucky
    • Lexington, Kentucky, United States, 40511-1093
      • Veterans Affairs Medical Center - Lexington
    • Lexington, Kentucky, United States, 40536-0084
      • Albert B. Chandler Medical Center, University of Kentucky
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University School of Medicine
    • New Orleans, Louisiana, United States, 70112
      • MBCCOP - LSU Health Sciences Center
    • Shreveport, Louisiana, United States, 71130-3932
      • Louisiana State University Health Sciences Center - Shreveport
    • Shreveport, Louisiana, United States, 71130
      • Veterans Affairs Medical Center - Shreveport
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
    • Jamaica Plain, Massachusetts, United States, 02130
      • Veterans Affairs Medical Center - Boston (Jamaica Plain)
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-0752
      • University of Michigan Comprehensive Cancer Center
    • Ann Arbor, Michigan, United States, 48105
      • Veterans Affairs Medical Center - Ann Arbor
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Detroit, Michigan, United States, 48201-1379
      • Barbara Ann Karmanos Cancer Institute
    • Detroit, Michigan, United States, 48201-1932
      • Veterans Affairs Medical Center - Detroit
    • Grand Rapids, Michigan, United States, 49503
      • CCOP - Grand Rapids Clinical Oncology Program
    • Southfield, Michigan, United States, 48075-9975
      • Providence Hospital - Southfield
  • Mississippi
    • Biloxi, Mississippi, United States, 39531-2410
      • Veterans Affairs Medical Center - Biloxi
    • Jackson, Mississippi, United States, 39216-4505
      • University of Mississippi Medical Center
    • Jackson, Mississippi, United States, 39216
      • Veterans Affairs Medical Center - Jackson
    • Keesler AFB, Mississippi, United States, 39534-2576
      • Keesler Medical Center - Keesler AFB
  • Missouri
    • Kansas City, Missouri, United States, 64128
      • Veterans Affairs Medical Center - Kansas City
    • Kansas City, Missouri, United States, 64131
      • CCOP - Kansas City
    • Saint Louis, Missouri, United States, 63110-0250
      • St. Louis University Health Sciences Center
    • Saint Louis, Missouri, United States, 63141
      • CCOP - St. Louis-Cape Girardeau
    • Springfield, Missouri, United States, 65807
      • CCOP - Cancer Research for the Ozarks
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
  • New Mexico
    • Albuquerque, New Mexico, United States, 87108-5138
      • Veterans Affairs Medical Center - Albuquerque
    • Albuquerque, New Mexico, United States, 87131
      • MBCCOP - University of New Mexico HSC
  • New York
    • New York, New York, United States, 10032
      • Herbert Irving Comprehensive Cancer Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Barrett Cancer Center, The University Hospital
    • Cincinnati, Ohio, United States, 45220-2288
      • Veterans Affairs Medical Center - Cincinnati
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
    • Columbus, Ohio, United States, 43206
      • CCOP - Columbus
    • Dayton, Ohio, United States, 45428
      • Veterans Affairs Medical Center - Dayton
    • Kettering, Ohio, United States, 45429
      • CCOP - Dayton
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma Medical Research Foundation
    • Oklahoma City, Oklahoma, United States, 73104
      • Veterans Affairs Medical Center - Oklahoma City
  • Oregon
    • Portland, Oregon, United States, 97207
      • Veterans Affairs Medical Center - Portland
    • Portland, Oregon, United States, 97213
      • CCOP - Columbia River Program
    • Portland, Oregon, United States, 97201-3098
      • Oregon Cancer Center
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • CCOP - Greenville
    • Spartanburg, South Carolina, United States, 29303
      • CCOP - Upstate Carolina
  • Texas
    • Dallas, Texas, United States, 75216
      • Veterans Affairs Medical Center - Dallas
    • Dallas, Texas, United States, 75235-9154
      • Simmons Cancer Center - Dallas
    • Fort Sam Houston, Texas, United States, 78234
      • Brooke Army Medical Center
    • Galveston, Texas, United States, 77555-0209
      • University of Texas Medical Branch
    • Lubbock, Texas, United States, 79423
      • Texas Tech University Health Science Center
    • San Antonio, Texas, United States, 78284-7811
      • University of Texas Health Science Center at San Antonio
    • San Antonio, Texas, United States, 78284
      • Veterans Affairs Medical Center - San Antonio (Murphy)
    • Temple, Texas, United States, 76504
      • Veterans Affairs Medical Center - Temple
    • Temple, Texas, United States, 76508
      • CCOP - Scott and White Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84148
      • Veterans Affairs Medical Center - Salt Lake City
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute
  • Washington
    • Seattle, Washington, United States, 98101
      • CCOP - Virginia Mason Research Center
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute
    • Seattle, Washington, United States, 98108
      • Veterans Affairs Medical Center - Seattle
    • Seattle, Washington, United States, 98109-1024
      • Fred Hutchinson Cancer Research Center
    • Tacoma, Washington, United States, 98405-0986
      • CCOP - Northwest

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

DISEASE CHARACTERISTICS: Histologically proven aggressive B-cell non-Hodgkin's lymphoma that has failed prior combination chemotherapy with an anthracycline-containing regimen Eligible histologies: Diffuse large cell Small non-cleaved cell/Burkitt's lymphoma No lymphoblastic or mantle cell lymphoma First relapse or primary refractory disease Ineligible for or refused treatment with salvage chemotherapy followed by high-dose therapy and autologous stem cell rescue Documented CD20 antigen expression Measurable disease No clinical evidence of CNS involvement by lymphoma

PATIENT CHARACTERISTICS: Age: Over 18 Performance status: Zubrod 0-2 Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Bilirubin no greater than 2 times upper limit of normal Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance greater than 60 mL/min Other: HIV negative Not pregnant or nursing Fertile patients must use effective contraception No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics No prior rituximab Chemotherapy: See Disease Characteristics Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified Other: Recovered from toxic effects of all prior therapy No other concurrent therapy unless disease progression occurs

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ICE Chemotherapy; Etoposide 100 mg/m2 IV Days 1-3 Carboplatin AUC=5 IV Day 2 Ifosfamide 5 g/m2 IV Day 2 Mesna 5 g/m2 IV Day 2 Filgrastim 5ug/kg/day SQ Days 5-12 Q 21 days x 3 cycles	Drug: carboplatin; Drug: etoposide; Drug: ifosfamide; Biological: filgrastim; 5 μg/kg/day subcutaneous injection on Days 5-12 every 21 days for 3 cycles.
Experimental: Rituximab-ICE Chemotherapy; Etoposide 100 mg/m2 IV Days 2-4 Carboplatin AUC=5 IV Day 3 Ifosfamide 5 g/m2 IV Day 3 Mesna 5 g/m2 IV Day 3 Filgrastim 5ug/kg/day SQ Days 6-13 Q 21 days x 3 cycles Rituximab 375 mg/m2 IV Days 1 and 8 Cycle 1 Rituximab 375 mg/m2 IV Day 1 Cycles 2-3	Drug: carboplatin; Drug: etoposide; Biological: rituximab; Drug: ifosfamide; Biological: filgrastim; 5 μg/kg/day subcutaneous injection on Days 5-12 every 21 days for 3 cycles.

Collaborators and Investigators

• Sponsor: Southwest Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: David G. Maloney, MD, PhD, Fred Hutchinson Cancer Center

Study record dates

Study Major Dates

• Study Start: October 1, 2000
• Primary Completion (Actual): November 1, 2002
• Study Completion (Actual): November 1, 2006

Study Registration Dates

• First Submitted: December 6, 2000
• First Submitted That Met QC Criteria: March 16, 2004
• First Posted (Estimate): March 17, 2004

Study Record Updates

• Last Update Posted (Estimate): April 10, 2013
• Last Update Submitted That Met QC Criteria: April 8, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: recurrent adult diffuse large cell lymphoma; recurrent adult Burkitt lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Carboplatin; Etoposide; Ifosfamide; Rituximab
• Other Study ID Numbers: CDR0000068320; U10CA032102 (U.S. NIH Grant/Contract); S0019 (Other Identifier: SWOG)