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)”

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

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.

Primary:

• Event-free survival at 2 years No

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

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  

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