Cyclophosphamide, Rituximab, and Either Prednisone or Methylprednisolone in Treating Patients With Lymphoproliferative Disease After Solid Organ Transplantation
Overview[ - collapse ][ - ]
| Purpose | 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. |
|---|---|
| Condition | Lymphoproliferative Disorder |
| Intervention | Biological: rituximab Drug: cyclophosphamide Drug: methylprednisolone Drug: prednisone |
| Phase | Phase 2 |
| Sponsor | Children's Oncology Group |
| Responsible Party | Children's Oncology Group |
| ClinicalTrials.gov Identifier | NCT00066469 |
| First Received | August 6, 2003 |
| Last Updated | December 3, 2013 |
| Last verified | December 2013 |
Tracking Information[ + expand ][ + ]
| First Received Date | August 6, 2003 |
|---|---|
| Last Updated Date | December 3, 2013 |
| Start Date | April 2004 |
| Estimated Primary Completion Date | Not Provided |
| Current Primary Outcome Measures | Event-free Survival [Time Frame: 2 years] [Designated as safety issue: No]Alive in continuous complete remission with functioning original allograft |
| Current Secondary Outcome Measures | Not Provided |
Descriptive Information[ + expand ][ + ]
| Brief Title | Cyclophosphamide, Rituximab, and Either Prednisone or Methylprednisolone in Treating Patients With Lymphoproliferative Disease After Solid Organ Transplantation |
|---|---|
| Official Title | Phase II Study of Cyclophosphamide, Prednisone and Rituximab (CPR) in Children, Adolescents and Young Adults With B-lymphocyte Antigen CD20 (CD20) Positive Post-Transplant Lymphoproliferative Disease (PTLD) Following Solid Organ Transplantation (SOT) |
| Brief Summary | 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. |
| 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. |
| Study Type | Interventional |
| Study Phase | Phase 2 |
| Study Design | Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment |
| Condition | Lymphoproliferative Disorder |
| Intervention | Biological: rituximab Cycles 1 and 2 only: Given IV Incremental: First dosage: < 21 years of age: 0.5mg/kg/hr (maximum of 50 mg/hr) for the 1st hour ≥ 21 years of age: 50 mg/hr for the 1st hour. Subsequent dosages: < 21 years of age: 1.0mg/kg/hr (maximum of 50 mg/hr) for the 1st hour ≥ 21 years of age: 100 mg/hr for the 1st hour. Days 1, 8 and 15. Other Names:
Given IV over 30-60 minutes Dose 600 mg/m2 in 50-250 mL of normal saline (NS) or Dextrose-Water 5%(D5W) (at a maximum concentration of 20 mg/ml) over 30-60 minutes on day 1 of each cycle Other Names:
Methylprednisolone 0.8 mg/kg IV over 12 hours on days 1,2,3,4 and 5 of each cycle. Other Names:
Dosage 1 mg/kg orally every 12 hours on days 1,2,3,4 and 5 of each cycle. Oral prednisone may be rounded up to the nearest 2.5 mg as necessary for tablet size Other Names:
|
| Study Arm (s) | Experimental: Cyclophosphamide, prednisone, rituximab 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 |
Recruitment Information[ + expand ][ + ]
| Recruitment Status | Active, not recruiting |
|---|---|
| Estimated Enrollment | 55 |
| Estimated Completion Date | Not Provided |
| Estimated Primary Completion Date | October 2009 |
| Eligibility 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 central nervous system (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 |
| Gender | Both |
| Ages | N/A |
| Accepts Healthy Volunteers | No |
| Contacts | Not Provided |
| Location Countries | United States, Australia, Canada, New Zealand |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT00066469 |
|---|---|
| Other Study ID Numbers | ANHL0221 |
| Has Data Monitoring Committee | Yes |
| Information Provided By | Children's Oncology Group |
| Study Sponsor | Children's Oncology Group |
| Collaborators | National Cancer Institute (NCI) |
| Investigators | Study Chair: Thomas G. Gross, MD, PhD Nationwide Children's Hospital |
| Verification Date | December 2013 |
Locations[ + expand ][ + ]
| Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham | Birmingham, Alabama, United States, 35294 |
|---|---|
| Phoenix Children's Hospital | Phoenix, Arizona, United States, 85016-7710 |
| Arkansas Cancer Research Center at University of Arkansas for Medical Sciences | Little Rock, Arkansas, United States, 72205 |
| Southern California Permanente Medical Group | Downey, California, United States, 90242-2814 |
| Loma Linda University Cancer Institute at Loma Linda University Medical Center | Loma Linda, California, United States, 92354 |
| Kaiser Permanente Medical Center - Oakland | Sacramento, California, United States, 95825 |
| UCSF Helen Diller Family Comprehensive Cancer Center | San Francisco, California, United States, 94115 |
| Stanford Cancer Center | Stanford, California, United States, 94305-5824 |
| Children's Hospital Center for Cancer and Blood Disorders | Aurora, Colorado, United States, 80045 |
| Alfred I. duPont Hospital for Children | Wilmington, Delaware, United States, 19803 |
| Lee Cancer Care of Lee Memorial Health System | Fort Myers, Florida, United States, 33901 |
| University of Florida Shands Cancer Center | Gainesville, Florida, United States, 32610-0232 |
| Nemours Children's Clinic | Jacksonville, Florida, United States, 32207 |
| University of Miami Sylvester Comprehensive Cancer Center - Miami | Miami, Florida, United States, 33136 |
| Sacred Heart Cancer Center at Sacred Heart Hospital | Pensacola, Florida, United States, 32504 |
| All Children's Hospital | St. Petersburg, Florida, United States, 33701 |
| Winship Cancer Institute of Emory University | Atlanta, Georgia, United States, 30322 |
| Children's Memorial Hospital - Chicago | Chicago, Illinois, United States, 60614 |
| University of Chicago Cancer Research Center | Chicago, Illinois, United States, 60637-1470 |
| University of Illinois Cancer Center | Chicago, Illinois, United States, 60612-7243 |
| Simmons Cooper Cancer Institute | Springfield, Illinois, United States, 62794-9677 |
| Indiana University Melvin and Bren Simon Cancer Center | Indianapolis, Indiana, United States, 46202-5289 |
| Kosair Children's Hospital | Louisville, Kentucky, United States, 40232 |
| Tulane Cancer Center Office of Clinical Research | Alexandria, Louisiana, United States, 71315-3198 |
| C.S. Mott Children's Hospital at University of Michigan Medical Center | Ann Arbor, Michigan, United States, 48109-0286 |
| Barbara Ann Karmanos Cancer Institute | Detroit, Michigan, United States, 48201-1379 |
| Butterworth Hospital at Spectrum Health | Grand Rapids, Michigan, United States, 49503-2560 |
| CCOP - Kalamazoo | Kalamazoo, Michigan, United States, 49007-5341 |
| Masonic Cancer Center at University of Minnesota | Minneapolis, Minnesota, United States, 55455 |
| Mayo Clinic Cancer Center | Rochester, Minnesota, United States, 55905 |
| University of Mississippi Cancer Clinic | Jackson, Mississippi, United States, 39216-4505 |
| Ellis Fischel Cancer Center at University of Missouri - Columbia | Columbia, Missouri, United States, 65203 |
| Children's Mercy Hospital | Kansas City, Missouri, United States, 64108 |
| Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis | St. Louis, Missouri, United States, 63110 |
| UNMC Eppley Cancer Center at the University of Nebraska Medical Center | Omaha, Nebraska, United States, 68198-6805 |
| Sunrise Hospital and Medical Center | Las Vegas, Nevada, United States, 89109-2306 |
| Hackensack University Medical Center Cancer Center | Hackensack, New Jersey, United States, 07601 |
| Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center | New York, New York, United States, 10032 |
| Mount Sinai Medical Center | New York, New York, United States, 10029 |
| James P. Wilmot Cancer Center at University of Rochester Medical Center | Rochester, New York, United States, 14642 |
| SUNY Upstate Medical University Hospital | Syracuse, New York, United States, 13210 |
| New York Medical College | Valhalla, New York, United States, 10595 |
| Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill | Chapel Hill, North Carolina, United States, 27599-7295 |
| Blumenthal Cancer Center at Carolinas Medical Center | Charlotte, North Carolina, United States, 28232-2861 |
| Akron Children's Hospital | Akron, Ohio, United States, 44308-1062 |
| Cincinnati Children's Hospital Medical Center | Cincinnati, Ohio, United States, 45229-3039 |
| Cleveland Clinic Taussig Cancer Center | Cleveland, Ohio, United States, 44195 |
| Rainbow Babies and Children's Hospital | Cleveland, Ohio, United States, 44106-5000 |
| Nationwide Children's Hospital | Columbus, Ohio, United States, 43205-2696 |
| Oklahoma University Cancer Institute | Oklahoma City, Oklahoma, United States, 73104 |
| Legacy Emanuel Hospital and Health Center and Children's Hospital | Portland, Oregon, United States, 97227 |
| Children's Hospital of Philadelphia | Philadelphia, Pennsylvania, United States, 19104-9786 |
| Children's Hospital of Pittsburgh | Pittsburgh, Pennsylvania, United States, 15213 |
| East Tennessee Children's Hospital | Knoxville, Tennessee, United States, 37901 |
| Vanderbilt-Ingram Cancer Center | Nashville, Tennessee, United States, 37232-6838 |
| Driscoll Children's Hospital | Corpus Christi, Texas, United States, 78411 |
| Medical City Dallas Hospital | Dallas, Texas, United States, 75230 |
| Methodist Children's Hospital of South Texas | San Antonio, Texas, United States, 78229-3993 |
| University of Texas Health Science Center at San Antonio | San Antonio, Texas, United States, 78207 |
| Primary Children's Medical Center | Salt Lake City, Utah, United States, 84113-1100 |
| Fletcher Allen Health Care - University Health Center Campus | Burlington, Vermont, United States, 05401 |
| Inova Fairfax Hospital | Falls Church, Virginia, United States, 22042-3300 |
| Children's Hospital of The King's Daughters | Norfolk, Virginia, United States, 23507-1971 |
| Children's Hospital and Regional Medical Center - Seattle | Seattle, Washington, United States, 98105 |
| West Virginia University Health Sciences Center - Charleston | Charleston, West Virginia, United States, 25302 |
| Marshfield Clinic - Marshfield Center | Marshfield, Wisconsin, United States, 54449 |
| Westmead Institute for Cancer Research at Westmead Hospital | Westmead, New South Wales, Australia, 2145 |
| Royal Children's Hospital | Brisbane, Queensland, Australia, 4029 |
| Princess Margaret Hospital for Children | Perth, Western Australia, Australia, 6001 |
| University of Alberta Hospital | Edmonton, Alberta, Canada, T6G 1Z2 |
| Children's & Women's Hospital of British Columbia | Vancouver, British Columbia, Canada, V6H 3V4 |
| CancerCare Manitoba | Winnipeg, Manitoba, Canada, R3E 0V9 |
| IWK Health Centre | Halifax, Nova Scotia, Canada, B3K 6R8 |
| Hospital for Sick Children | Toronto, Ontario, Canada, M5G 1X8 |
| Hopital Sainte Justine | Montreal, Quebec, Canada, H3T 1C5 |
| Montreal Children's Hospital at McGill University Health Center | Montreal, Quebec, Canada, H3H 1P3 |
| Starship Children's Health | Auckland, New Zealand, 1 |
| Christchurch Hospital | Christchurch, New Zealand |