Overview

This trial is active, not recruiting.

Condition lymphoproliferative disorder
Treatments rituximab, cyclophosphamide, methylprednisolone, prednisone
Phase phase 2
Target CD20
Sponsor Children's Oncology Group
Collaborator National Cancer Institute (NCI)
Start date April 2004
End date October 2009
Trial size 55 participants
Trial identifier NCT00066469, ANHL0221, CDR0000316241, COG-ANHL0221, NCI-2012-02544, U10CA098543

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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
rituximab 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.
cyclophosphamide Cytoxan
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
methylprednisolone Deltaone
Methylprednisolone 0.8 mg/kg IV over 12 hours on days 1,2,3,4 and 5 of each cycle.
prednisone Deltaone
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

Primary Outcomes

Measure
Event-free Survival
time frame: 2 years

Eligibility Criteria

Male or female participants up to 30 years old.

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

Additional Information

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)
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.
Trial information was received from ClinicalTrials.gov and was last updated in September 2015.
Information provided to ClinicalTrials.gov by Children's Oncology Group.