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)
N/A
30 Years
Both
Lymphoproliferative Disorder
Trial Information
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)
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Event-free survival at 2 years
Outcome Description:
Estimated by Kaplan-Meier method. The correlation between outcome (EFS or OS) and covariates such as EBV viral load, EBV-CTL, subsets of PBL, dendritic cells in peripheral blood, and peripheral blood levels of Rituximab will be evaluated using the proportional hazards model. The correlation between gene expression and survival will also be evaluated using the proportional hazards model
Outcome Time Frame:
2 years
Safety Issue:
No
Principal Investigator
Thomas G. Gross, MD, PhD
Investigator Role:
Study Chair
Investigator Affiliation:
Nationwide Children's Hospital
Authority:
United States: Federal Government
Study ID:
ANHL0221
NCT ID:
NCT00066469
Start Date:
April 2004
Completion Date:
Related Keywords:
- Lymphoproliferative Disorder
- post-transplant lymphoproliferative disorder
- Lymphoproliferative Disorders
Name | Location |
|---|---|
| Children's Hospital of Philadelphia | Philadelphia, Pennsylvania 19104 |
| Mayo Clinic Cancer Center | Rochester, Minnesota 55905 |
| University of Chicago Cancer Research Center | Chicago, Illinois 60637 |
| Barbara Ann Karmanos Cancer Institute | Detroit, Michigan 48201 |
| Medical City Dallas Hospital | Dallas, Texas 75230 |
| University of Texas Health Science Center at San Antonio | San Antonio, Texas 78284-7811 |
| CCOP - Kalamazoo | Kalamazoo, Michigan 49007-3731 |
| Vanderbilt-Ingram Cancer Center | Nashville, Tennessee 37232-6838 |
| Marshfield Clinic - Marshfield Center | Marshfield, Wisconsin 54449 |
| New York Medical College | Valhalla, New York 10595 |
| Ellis Fischel Cancer Center at University of Missouri - Columbia | Columbia, Missouri 65203 |
| Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill | Chapel Hill, North Carolina 27599-7570 |
| Cleveland Clinic Taussig Cancer Center | Cleveland, Ohio 44195 |
| Children's Mercy Hospital | Kansas City, Missouri 64108 |
| Children's Hospital of Pittsburgh | Pittsburgh, Pennsylvania 15213 |
| Children's Hospital and Regional Medical Center - Seattle | Seattle, Washington 98105 |
| Nemours Children's Clinic | Jacksonville, Florida 32207 |
| All Children's Hospital | St. Petersburg, Florida 33701 |
| Children's Memorial Hospital - Chicago | Chicago, Illinois 60614 |
| Driscoll Children's Hospital | Corpus Christi, Texas 78466 |
| Inova Fairfax Hospital | Falls Church, Virginia 22042-3300 |
| Fletcher Allen Health Care - University Health Center Campus | Burlington, Vermont 05401 |
| Phoenix Children's Hospital | Phoenix, Arizona 85016-7710 |
| Southern California Permanente Medical Group | Downey, California 90242 |
| Kosair Children's Hospital | Louisville, Kentucky 40202-3830 |
| Sunrise Hospital and Medical Center | Las Vegas, Nevada 89109-2306 |
| East Tennessee Children's Hospital | Knoxville, Tennessee 37901 |
| Children's Hospital of the King's Daughters | Norfolk, Virginia 23507 |
| Arkansas Cancer Research Center at University of Arkansas for Medical Sciences | Little Rock, Arkansas 72205 |
| Blumenthal Cancer Center at Carolinas Medical Center | Charlotte, North Carolina 28232-2861 |
| Loma Linda University Cancer Institute at Loma Linda University Medical Center | Loma Linda, California 92354 |
| Kaiser Permanente Medical Center - Oakland | Sacramento, California 95825 |
| Lee Cancer Care of Lee Memorial Health System | Fort Myers, Florida 33901 |
| University of Florida Shands Cancer Center | Gainesville, Florida 32610-0232 |
| Sacred Heart Cancer Center at Sacred Heart Hospital | Pensacola, Florida 32504 |
| Winship Cancer Institute of Emory University | Atlanta, Georgia 30322 |
| Hackensack University Medical Center Cancer Center | Hackensack, New Jersey 07601 |
| Mount Sinai Medical Center | New York, New York 10029 |
| SUNY Upstate Medical University Hospital | Syracuse, New York 13210 |
| Cincinnati Children's Hospital Medical Center | Cincinnati, Ohio 45229-3039 |
| Rainbow Babies and Children's Hospital | Cleveland, Ohio 44106-5000 |
| Methodist Children's Hospital of South Texas | San Antonio, Texas 78229-3993 |
| Primary Children's Medical Center | Salt Lake City, Utah 84113-1100 |
| James P. Wilmot Cancer Center at University of Rochester Medical Center | Rochester, New York 14642 |
| UNMC Eppley Cancer Center at the University of Nebraska Medical Center | Omaha, Nebraska 68198-7680 |
| UCSF Helen Diller Family Comprehensive Cancer Center | San Francisco, California 94115 |
| Children's Hospital Center for Cancer and Blood Disorders | Aurora, Colorado 80045 |
| Alfred I. duPont Hospital for Children | Wilmington, Delaware 19803 |
| University of Illinois Cancer Center | Chicago, Illinois 60612-7243 |
| Simmons Cooper Cancer Institute | Springfield, Illinois 62794-9677 |
| Indiana University Melvin and Bren Simon Cancer Center | Indianapolis, Indiana 46202-5289 |
| Tulane Cancer Center Office of Clinical Research | Alexandria, Louisiana 71315-3198 |
| C.S. Mott Children's Hospital at University of Michigan Medical Center | Ann Arbor, Michigan 48109-0286 |
| Butterworth Hospital at Spectrum Health | Grand Rapids, Michigan 49503-2560 |
| Masonic Cancer Center at University of Minnesota | Minneapolis, Minnesota 55455 |
| University of Mississippi Cancer Clinic | Jackson, Mississippi 39216-4505 |
| Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis | St. Louis, Missouri 63110 |
| Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center | New York, New York 10032 |
| Akron Children's Hospital | Akron, Ohio 44308-1062 |
| Nationwide Children's Hospital | Columbus, Ohio 43205-2696 |
| Oklahoma University Cancer Institute | Oklahoma City, Oklahoma 73104 |
| Legacy Emanuel Hospital and Health Center and Children's Hospital | Portland, Oregon 97227 |
| West Virginia University Health Sciences Center - Charleston | Charleston, West Virginia 25302 |
| Stanford Cancer Center | Stanford, California 94305-5824 |
| University of Miami Sylvester Comprehensive Cancer Center - Miami | Miami, Florida 33136 |
| Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham | Birmingham, Alabama 35294 |
