Cyclophosphamide, Rituximab, and Either Prednisone or Methylprednisolone in Treating Patients With Lymphoproliferative Disease After Solid Organ Transplantation

Condition(s) targeted: Lymphoma

Intervention: cyclophosphamide (Drug); methylprednisolone (Drug); prednisone (Drug); rituximab (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Children's Oncology Group

Official(s) and/or principal investigator(s):
Thomas G. Gross, MD, PhD, Study Chair, Affiliation: Nationwide Children's Hospital

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.

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)

Study design: Treatment, Open Label

Primary outcome: Event-free survival at 2 years

Detailed 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.

Minimum age: N/A. Maximum age: 30 Years. Gender(s): Both.

Criteria:

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

Christchurch Hospital, Christchurch, New Zealand; Recruiting
Robin P. Corbett, Phone: 643364-0740

Starship Children's Health, Auckland 1, New Zealand; Recruiting
Lochie Teague, Phone: 64930749496368

Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham, Birmingham, Alabama 35294, United States; Recruiting
Clinical Trials Office - Lurleen Wallace Comprehensive Cancer, Phone: 205-934-0309

University of Alberta Hospital, Edmonton, Alberta T6G 1Z2, Canada; Recruiting
Sunil Desai, Phone: 780-407-8829

Phoenix Children's Hospital, Phoenix, Arizona 85016-7710, United States; Recruiting
Jessica L. Boklan, Phone: 602-546-0920

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, United States; Recruiting
Clinical Trial Office - Arkansas Cancer Research Center at Uni, Phone: 501-686-8274

Children's & Women's Hospital of British Columbia, Vancouver, British Columbia V6H 3V4, Canada; Recruiting
Mason Bond, Phone: 604-875-2322

Kaiser Permanente Medical Center - Oakland, Sacramento, California 95825, United States; Recruiting
Vincent Kiley, Phone: 916-973-7331

Loma Linda University Cancer Institute at Loma Linda University Medical Center, Loma Linda, California 92354, United States; Recruiting
Clinical Trials Office - Loma Linda University Cancer Institut, Phone: 909-558-3375

Southern California Permanente Medical Group, Downey, California 90242-2814, United States; Recruiting
Robert Cooper, Phone: 323-783-5307

Stanford Cancer Center, Stanford, California 94305-5824, United States; Recruiting
Clinical Trials Office - Stanford Cancer Center, Phone: 650-498-7061, Email: cctoffice@stanford.edu

UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California 94115, United States; Recruiting
Clinical Trials Office - UCSF Helen Diller Family Comprehensi, Phone: 877-827-3222

Children's Hospital Center for Cancer and Blood Disorders, Aurora, Colorado 80045, United States; Recruiting
Kelly Maloney, Phone: 720-777-6673

Alfred I. duPont Hospital for Children, Wilmington, Delaware 19803, United States; Recruiting
Clinical Trials Office - Alfred I. duPont Hospital for Childre, Phone: 302-651-5755

All Children's Hospital, St. Petersburg, Florida 33701, United States; Recruiting
Jerry Barbosa, Phone: 727-767-4176

Lee Cancer Care of Lee Memorial Health System, Fort Myers, Florida 33901, United States; Recruiting
Clinical Trials Office - Lee Cancer Care of Lee Memorial Healt, Phone: 877-680-0008

Nemours Children's Clinic, Jacksonville, Florida 32207, United States; Recruiting
Eric Sandler, Phone: 904-390-3793

Sacred Heart Cancer Center at Sacred Heart Hospital, Pensacola, Florida 32504, United States; Recruiting
Clinical Trials Office - Sacred Heart Cancer Center, Phone: 850-416-4611

University of Florida Shands Cancer Center, Gainesville, Florida 32610-0232, United States; Recruiting
Clinical Trials Office - University of Florida Shands Cancer C, Phone: 888-254-7581

University of Miami Sylvester Comprehensive Cancer Center - Miami, Miami, Florida 33136, United States; Recruiting
University of Miami Sylvester Comprehensive Cancer Center Clin, Phone: 866-574-5124, Email: Sylvester@emergingmed.com

Winship Cancer Institute of Emory University, Atlanta, Georgia 30322, United States; Recruiting
Howard M. Katzenstein, Phone: 404-785-0853

Children's Memorial Hospital - Chicago, Chicago, Illinois 60614, United States; Recruiting
David O. Walterhouse, Phone: 773-755-6514

Simmons Cooper Cancer Institute, Springfield, Illinois 62794-9677, United States; Recruiting
Clinical Trials Office - Simmons Cooper Cancer Institute, Phone: 217-545-7929

University of Chicago Cancer Research Center, Chicago, Illinois 60637-1470, United States; Recruiting
Clinical Trials Office - University of Chicago Cancer Research, Phone: 773-834-7424

University of Illinois Cancer Center, Chicago, Illinois 60612-7243, United States; Recruiting
Clinical Trial Office - University of Illinois Cancer Center, Phone: 312-355-3046

Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana 46202-5289, United States; Recruiting
Clinical Trials Office - Indiana University Cancer Center, Phone: 317-274-2552

Kosair Children's Hospital, Louisville, Kentucky 40232, United States; Recruiting
Clinical Trials Office - Kosair Children's Hospital, Phone: 502-629-5500, Email: CancerResource@nortonhealthcare.org

Tulane Cancer Center Office of Clinical Research, Alexandria, Louisiana 71315-3198, United States; Recruiting
Clinical Trials Office - Tulane Cancer Center, Phone: 504-988-6121

CancerCare Manitoba, Winnipeg, Manitoba R3E 0V9, Canada; Recruiting
Rochelle Yanofsky, Phone: 204-787-4163

Barbara Ann Karmanos Cancer Institute, Detroit, Michigan 48201-1379, United States; Recruiting
Clinical Trials Office - Barbara Ann Karmanos Cancer Institute, Phone: 313-576-9363

Butterworth Hospital at Spectrum Health, Grand Rapids, Michigan 49503-2560, United States; Recruiting
David S. Dickens, Phone: 616-391-2086

C.S. Mott Children's Hospital at University of Michigan Medical Center, Ann Arbor, Michigan 48109-0286, United States; Recruiting
Clinical Trials Office - C.S. Mott Children's Hospital, Phone: 800-865-1125

CCOP - Kalamazoo, Kalamazoo, Michigan 49007-5341, United States; Recruiting
Leonard A. Mattano, Jr., Phone: 269-341-6350

Masonic Cancer Center at University of Minnesota, Minneapolis, Minnesota 55455, United States; Recruiting
Clinical Trials Office - Masonic Cancer Center at University o, Phone: 612-624-2620

Mayo Clinic Cancer Center, Rochester, Minnesota 55905, United States; Recruiting
Clinical Trials Office - All Mayo Clinic Locations, Phone: 507-538-7623

University of Mississippi Cancer Clinic, Jackson, Mississippi 39216-4505, United States; Recruiting
Gail C. Megason, Phone: 601-984-5220

Children's Mercy Hospital, Kansas City, Missouri 64108, United States; Recruiting
Maxine Hetherington, Phone: 816-234-3265

Ellis Fischel Cancer Center at University of Missouri - Columbia, Columbia, Missouri 65203, United States; Recruiting
Clinical Trial Office - Ellis Fischel Cancer Center, Phone: 573-882-4894

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis, St. Louis, Missouri 63110, United States; Recruiting
Robert J. Hayashi, Phone: 314-454-4118

UNMC Eppley Cancer Center at the University of Nebraska Medical Center, Omaha, Nebraska 68198-6805, United States; Recruiting
Clinical Trials Office - UNMC Eppley Cancer Center at the Univ, Phone: 800-999-5465

Sunrise Hospital and Medical Center, Las Vegas, Nevada 89109-2306, United States; Recruiting
Jonathan Bernstein, Phone: 702-732-1493

Hackensack University Medical Center Cancer Center, Hackensack, New Jersey 07601, United States; Recruiting
Clinical Trials Office - Hackensack University Medical Center, Phone: 201-996-2879

Westmead Institute for Cancer Research at Westmead Hospital, Westmead, New South Wales 2145, Australia; Recruiting
Geoffrey McCowage, Phone: 61298452122

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center, New York, New York 10032, United States; Recruiting
Clinical Trials Office - Herbert Irving Comprehensive Cancer C, Phone: 212-305-8615

James P. Wilmot Cancer Center at University of Rochester Medical Center, Rochester, New York 14642, United States; Recruiting
Barbara L. Asselin, Phone: 585-275-2981

Mount Sinai Medical Center, New York, New York 10029, United States; Recruiting
Birte Wistinghausen, Phone: 212-241-7022

New York Medical College, Valhalla, New York 10595, United States; Recruiting
Fevzi Ozkaynak, Phone: 914-493-7997

SUNY Upstate Medical University Hospital, Syracuse, New York 13210, United States; Recruiting
Clinical Trials Office - SUNY Upstate Medical University Hospi, Phone: 315-464-5476

Blumenthal Cancer Center at Carolinas Medical Center, Charlotte, North Carolina 28232-2861, United States; Recruiting
Clinical Trials Office - Blumenthal Cancer Center at Carolinas, Phone: 704-355-2884

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill, Chapel Hill, North Carolina 27599-7295, United States; Recruiting
Clinical Trials Office - Lineberger Comprehensive Cancer Cente, Phone: 877-668-0683; 919-966-4432

IWK Health Centre, Halifax, Nova Scotia B3K 6R8, Canada; Recruiting
Margaret C. Yhap, Phone: 902-470-8778

Akron Children's Hospital, Akron, Ohio 44308-1062, United States; Recruiting
Clinical Trials Office - Akron Children's Hospital, Phone: 330-543-3193

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, United States; Recruiting
Clinical Trials Office - Cincinnati Children's Hospital Medica, Phone: 513-636-0161

Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio 44195, United States; Recruiting
Clinical Trials Office - Cleveland Clinic Taussig Cancer Cente, Phone: 866-223-8100

Nationwide Children's Hospital, Columbus, Ohio 43205-2696, United States; Recruiting
Amanda Termuhlen, Phone: 614-722-3552

Rainbow Babies and Children's Hospital, Cleveland, Ohio 44106-5000, United States; Recruiting
Susan Wiersma, Phone: 216-844-3345

Oklahoma University Cancer Institute, Oklahoma City, Oklahoma 73104, United States; Recruiting
Rene Y. McNall-Knapp, Phone: 405-271-5311

Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada; Recruiting
Ronald M. Grant, Phone: 416-813-8885

Legacy Emanuel Hospital and Health Center and Children's Hospital, Portland, Oregon 97227, United States; Recruiting
Clinical Trials Office - Legacy Emanuel Hospital and Health Ce, Phone: 503-413-8199

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104-9786, United States; Recruiting
Peter Adamson, Phone: 215-590-6359

Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States; Recruiting
Clinical Trials Office - Children's Hospital of Pittsburgh, Phone: 412-692-5573

Hopital Sainte Justine, Montreal, Quebec H3T 1C5, Canada; Recruiting
Albert Moghrabi, Phone: 514-345-4969

Montreal Children's Hospital at McGill University Health Center, Montreal, Quebec H3H 1P3, Canada; Recruiting
Sharon Abish, Phone: 514-412-4400x22219

Royal Children's Hospital, Brisbane, Queensland 4029, Australia; Recruiting
Helen Irving, Phone: 617-3636-8671

Hollings Cancer Center at Medical University of South Carolina, Charleston, South Carolina 29425, United States; Recruiting
Clinical Trials Office - Hollings Cancer Center at Medical Uni, Phone: 843-792-9321

East Tennessee Children's Hospital, Knoxville, Tennessee 37901, United States; Recruiting
Ray C. Pais, Phone: 865-541-8266

Vanderbilt-Ingram Cancer Center, Nashville, Tennessee 37232-6838, United States; Recruiting
Clinical Trials Office - Vanderbilt-Ingram Cancer Center, Phone: 800-811-8480

Driscoll Children's Hospital, Corpus Christi, Texas 78411, United States; Recruiting
Clinical Trials Office - Driscoll Children's Hospital, Phone: 361-694-5311

Medical City Dallas Hospital, Dallas, Texas 75230, United States; Recruiting
Carl Lenarsky, Phone: 972-566-6647x4439

Methodist Children's Hospital of South Texas, San Antonio, Texas 78229-3993, United States; Recruiting
Michael S. Grimley, Phone: 210-575-7268

University of Texas Health Science Center at San Antonio, San Antonio, Texas 78207, United States; Recruiting
Paul Thomas, Phone: 210-704-2187

Primary Children's Medical Center, Salt Lake City, Utah 84113-1100, United States; Recruiting
Phillip E. Barnette, Phone: 801-662-4700

Fletcher Allen Health Care - University Health Center Campus, Burlington, Vermont 05401, United States; Recruiting
Clinical Trials Office - Fletcher Allen Health Care, Phone: 802-656-8990

Children's Hospital of The King's Daughters, Norfolk, Virginia 23507-1971, United States; Recruiting
Eric J. Lowe, Phone: 757-668-7243

Inova Fairfax Hospital, Falls Church, Virginia 22042-3300, United States; Recruiting
Clinical Trials Office - Inova Fairfax Hospital, Phone: 703-208-6650

Children's Hospital and Regional Medical Center - Seattle, Seattle, Washington 98105, United States; Recruiting
Douglas Hawkins, Phone: 206-987-3096

West Virginia University Health Sciences Center - Charleston, Charleston, West Virginia 25302, United States; Recruiting
Elizabeth Kurczynski, Phone: 304-388-1540

Princess Margaret Hospital for Children, Perth, Western Australia 6001, Australia; Recruiting
Catherine Cole, Phone: 011-6189340-8238

Marshfield Clinic - Marshfield Center, Marshfield, Wisconsin 54449, United States; Recruiting
Clinical Trials Office - Marshfield Clinic - Marshfield Center, Phone: 800-782-1581 ext. 94457

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: April 2004
Last updated: June 11, 2008