Cyclophosphamide, Rituximab, and Either Prednisone or Methylprednisolone in Treating Patients With Lymphoproliferative Disease After Solid Organ Transplantation
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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 | Intervention | Phase |
|---|---|---|
|
Lymphoproliferative Disorder |
Biological: rituximab Drug: cyclophosphamide Drug: methylprednisolone Drug: prednisone |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| 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) |
- Event-free survival at 2 years [ Time Frame: 2 years ] [ Designated as safety issue: No ]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
| Enrollment: | 55 |
| Study Start Date: | April 2004 |
| Primary Completion Date: | October 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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
|
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:
Drug: cyclophosphamide
Given IV over 30-60 minutes Dose 600 mg/m2 in 50-250 mL of NS or D5W (at a maximum concentration of 20 mg/ml) over 30-60 minutes on day 1 of each cycle
Other Names:
Drug: methylprednisolone
Methylprednisolone 0.8 mg/kg IV over 12 hours on days 1,2,3,4 and 5 of each cycle.
Other Names:
Drug: prednisone
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:
|
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.
Eligibility| Ages Eligible for Study: | up to 30 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | 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
Contacts and Locations
Show 78 Study Locations| Study Chair: | Thomas G. Gross, MD, PhD | Nationwide Children's Hospital |
More Information
Additional Information:
Publications:
| Responsible Party: | Children's Oncology Group |
| ClinicalTrials.gov Identifier: | NCT00066469 History of Changes |
| Other Study ID Numbers: | ANHL0221, CDR0000316241, COG-ANHL0221, NCI-2012-02544, U10CA098543 |
| Study First Received: | August 6, 2003 |
| Last Updated: | March 12, 2013 |
| Health Authority: | United States: Federal Government |
Keywords provided by Children's Oncology Group:
|
post-transplant lymphoproliferative disorder |
Additional relevant MeSH terms:
|
Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Cyclophosphamide Rituximab Methylprednisolone Hemisuccinate Prednisolone Prednisone Methylprednisolone acetate Prednisolone acetate Methylprednisolone Prednisolone hemisuccinate Prednisolone phosphate Immunosuppressive Agents |
Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antirheumatic Agents Therapeutic Uses Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Central Nervous System Agents |
ClinicalTrials.gov processed this record on May 23, 2013