RATIONALE: Drugs used in chemotherapy such as cyclophosphamide, prednisone, and methylprednisolone 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. Combining cyclophosphamide and either prednisone or...
Date First Received: August 6, 2003
Last Updated: July 10, 2008
Verified by: National Cancer Institute (NCI), June 2008
Clinical Trial Phase: Phase 2 | Start Date: April 2004
Overall Status: Active, not recruiting
Estimated Enrollment: 60
Brief Summary
Official Title: “A Phase II Study of the Combination of Cyclophosphamide, Prednisone and Rituximab (CPR) in Children, Adolescents and Young Adults With CD20 Positive Post-Transplant Lymphoproliferative Disease (PTLD) Following Solid Organ Transplantation (SOT)”
Condition Keyword(s):
Intervention(s):
RATIONALE: Drugs used in chemotherapy such as cyclophosphamide, prednisone, and methylprednisolone 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. Combining cyclophosphamide and either prednisone or methylprednisolone with rituximab may be effective in treating lymphoproliferative disease following organ transplantation.
PURPOSE: Phase II trial to study the effectiveness of combining cyclophosphamide and either prednisone or methylprednisolone with rituximab in treating patients who have Epstein-Barr virus-positive lymphoproliferative disease following organ transplantation.
Study Type: Interventional
Study Design: Treatment, Open Label
Detailed Clinical Trial Description
OBJECTIVES: - Determine the safety and toxicity of cyclophosphamide, rituximab, and prednisone or methylprednisolone in patients with CD20-positive and Epstein-Barr virus-positive post-transplant lymphoproliferative disease (PTLD) after solid organ transplantation. - Determine the 2-year event-free survival, defined as alive and in continuous complete remission with a functioning original allograft, of patients treated with this regimen. - Determine the response rate in patients treated with this regimen. - Determine the PTLD gene expression profile by microarray analysis and fluorescent in situ hybridization in patients treated with this regimen. - Determine the accrual rate of patients to this study.
OUTLINE: This is a multicenter study.
Patients receive cyclophosphamide IV over 30-60 minutes on day 1 and oral prednisone or methylprednisolone IV twice daily on days 1-5. During courses 1 and 2 only, patients also receive rituximab IV over 2-5 hours on days 1, 8, and 15. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression, a new primary or secondary malignancy, or unrelated disease.
After finishing study treatment, patients are followed periodically for at least 5 years.
PROJECTED ACCRUAL: A total of 60 patients (50 with non-fulminant post-transplant lymphoproliferative disease [PTLD] and 10 fulminant PTLD) will be accrued for this study within 2.5-3 years.
Outcome Measures for this Clinical Trial
Primary:
- Event-free survival at 2 years No
Criteria for Participation in this Clinical Trial
DISEASE CHARACTERISTICS:
- Histologically confirmed post-transplant lymphoproliferative disease (PTLD)
- Presents with 1 of the following:
- Fulminant PTLD (F-PTLD)
- Fever greater than 38°C
- Hypotensive (for age)
- Evidence of multiple organ involvement/failure, including at least 2 of the following:
- Marrow (including pancytopenia without detectable B-cell proliferation)
- Liver (coagulopathy, transaminitis, and/or hyperbilirubinemia)
- Lungs (interstitial pneumonitis with or without pleural effusions)
- Gastrointestinal tract hemorrhage
- Non-fulminant PTLD (NF-PTLD)
- Does not meet the above F-PTLD criteria
- Considered medically refractory to reduced immune suppression (50% or more reduction of immunosuppression) for at least 1 week
- CD20 positive AND Epstein-Barr virus positive
- Must have received prior solid organ transplantation
- Must have residual disease after biopsy and/or surgery
- No PTLD CNS disease, defined as positive cytology and/or radiographic evidence
PATIENT CHARACTERISTICS:
- Age
- Under 31
- Performance status
- Not specified
- Life expectancy
- NF-PTLD patients:
- At least 8 weeks
- Hematopoietic
- See Disease Characteristics
- Hepatic
- See Disease Characteristics
- Renal
- Not specified
- Pulmonary
- See Disease Characteristics
- Other
- Not pregnant or nursing
- Fertile patients must use effective contraception
- HIV negative
PRIOR CONCURRENT THERAPY:
- Biologic therapy
- More than 1 month since prior rituximab
- Chemotherapy
- More than 4 weeks since prior chemotherapy and recovered
- Endocrine therapy
- Not specified
- Radiotherapy
- Not specified
- Surgery
- See Disease Characteristics
Clinical Trials Locations, Contact Details, and Sponsors
Lead Sponsor: Children's Oncology Group
Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
Birmingham Alabama 35294 United States
Phoenix Children's Hospital
Phoenix Arizona 85016-7710 United States
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock Arkansas 72205 United States
Kaiser Permanente Medical Center - Oakland
Sacramento California 95825 United States
Loma Linda University Cancer Institute at Loma Linda University Medical Center
Loma Linda California 92354 United States
Southern California Permanente Medical Group
Downey California 90242-2814 United States
Stanford Cancer Center
Stanford California 94305-5824 United States
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco California 94115 United States
Children's Hospital Center for Cancer and Blood Disorders
Aurora Colorado 80045 United States
Alfred I. duPont Hospital for Children
Wilmington Delaware 19803 United States
All Children's Hospital
St. Petersburg Florida 33701 United States
Lee Cancer Care of Lee Memorial Health System
Fort Myers Florida 33901 United States
Nemours Children's Clinic
Jacksonville Florida 32207 United States
Sacred Heart Cancer Center at Sacred Heart Hospital
Pensacola Florida 32504 United States
University of Florida Shands Cancer Center
Gainesville Florida 32610-0232 United States
University of Miami Sylvester Comprehensive Cancer Center - Miami
Miami Florida 33136 United States
Winship Cancer Institute of Emory University
Atlanta Georgia 30322 United States
Children's Memorial Hospital - Chicago
Chicago Illinois 60614 United States
Simmons Cooper Cancer Institute
Springfield Illinois 62794-9677 United States
University of Chicago Cancer Research Center
Chicago Illinois 60637-1470 United States
University of Illinois Cancer Center
Chicago Illinois 60612-7243 United States
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis Indiana 46202-5289 United States
Kosair Children's Hospital
Louisville Kentucky 40232 United States
Tulane Cancer Center Office of Clinical Research
Alexandria Louisiana 71315-3198 United States
Barbara Ann Karmanos Cancer Institute
Detroit Michigan 48201-1379 United States
Butterworth Hospital at Spectrum Health
Grand Rapids Michigan 49503-2560 United States
C.S. Mott Children's Hospital at University of Michigan Medical Center
Ann Arbor Michigan 48109-0286 United States
CCOP - Kalamazoo
Kalamazoo Michigan 49007-5341 United States
Masonic Cancer Center at University of Minnesota
Minneapolis Minnesota 55455 United States
Mayo Clinic Cancer Center
Rochester Minnesota 55905 United States
University of Mississippi Cancer Clinic
Jackson Mississippi 39216-4505 United States
Children's Mercy Hospital
Kansas City Missouri 64108 United States
Ellis Fischel Cancer Center at University of Missouri - Columbia
Columbia Missouri 65203 United States
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
St. Louis Missouri 63110 United States
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
Omaha Nebraska 68198-6805 United States
Sunrise Hospital and Medical Center
Las Vegas Nevada 89109-2306 United States
Hackensack University Medical Center Cancer Center
Hackensack New Jersey 07601 United States
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
New York New York 10032 United States
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester New York 14642 United States
Mount Sinai Medical Center
New York New York 10029 United States
New York Medical College
Valhalla New York 10595 United States
SUNY Upstate Medical University Hospital
Syracuse New York 13210 United States
Blumenthal Cancer Center at Carolinas Medical Center
Charlotte North Carolina 28232-2861 United States
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill North Carolina 27599-7295 United States
Akron Children's Hospital
Akron Ohio 44308-1062 United States
Cincinnati Children's Hospital Medical Center
Cincinnati Ohio 45229-3039 United States
Cleveland Clinic Taussig Cancer Center
Cleveland Ohio 44195 United States
Nationwide Children's Hospital
Columbus Ohio 43205-2696 United States
Rainbow Babies and Children's Hospital
Cleveland Ohio 44106-5000 United States
Oklahoma University Cancer Institute
Oklahoma City Oklahoma 73104 United States
Legacy Emanuel Hospital and Health Center and Children's Hospital
Portland Oregon 97227 United States
Children's Hospital of Philadelphia
Philadelphia Pennsylvania 19104-9786 United States
Children's Hospital of Pittsburgh
Pittsburgh Pennsylvania 15213 United States
East Tennessee Children's Hospital
Knoxville Tennessee 37901 United States
Vanderbilt-Ingram Cancer Center
Nashville Tennessee 37232-6838 United States
Driscoll Children's Hospital
Corpus Christi Texas 78411 United States
Medical City Dallas Hospital
Dallas Texas 75230 United States
Methodist Children's Hospital of South Texas
San Antonio Texas 78229-3993 United States
University of Texas Health Science Center at San Antonio
San Antonio Texas 78207 United States
Primary Children's Medical Center
Salt Lake City Utah 84113-1100 United States
Fletcher Allen Health Care - University Health Center Campus
Burlington Vermont 05401 United States
Children's Hospital of The King's Daughters
Norfolk Virginia 23507-1971 United States
Inova Fairfax Hospital
Falls Church Virginia 22042-3300 United States
Children's Hospital and Regional Medical Center - Seattle
Seattle Washington 98105 United States
West Virginia University Health Sciences Center - Charleston
Charleston West Virginia 25302 United States
Marshfield Clinic - Marshfield Center
Marshfield Wisconsin 54449 United States
Westmead Institute for Cancer Research at Westmead Hospital
Westmead New South Wales 2145 Australia
Royal Children's Hospital
Brisbane Queensland 4029 Australia
Princess Margaret Hospital for Children
Perth Western Australia 6001 Australia
University of Alberta Hospital
Edmonton Alberta T6G 1Z2 Canada
Children's & Women's Hospital of British Columbia
Vancouver British Columbia V6H 3V4 Canada
CancerCare Manitoba
Winnipeg Manitoba R3E 0V9 Canada
IWK Health Centre
Halifax Nova Scotia B3K 6R8 Canada
Hospital for Sick Children
Toronto Ontario M5G 1X8 Canada
Hopital Sainte Justine
Montreal Quebec H3T 1C5 Canada
Montreal Children's Hospital at McGill University Health Center
Montreal Quebec H3H 1P3 Canada
Christchurch Hospital
Christchurch New Zealand
Starship Children's Health
Auckland 1 New Zealand
Overall Clinical Trial Officials and Contacts
Thomas G. Gross, MD, PhD Study Chair Nationwide Children's Hospital
Additional Information
Information obtained from ClinicalTrials.gov on July 23, 2008
Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00066469
Study ID Number: CDR0000316241
ClinicalTrials.gov Identifier: NCT00066469
Health Authority: United States: Federal Government
Clinical trial summary from the National Cancer Institute's PDQ® database
Clinical Trials Authorship and Review
Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.