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)”

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.

Study Type: Interventional

Study Design: Treatment, Open Label

Study Primary Completion Date: July 2008

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.

Intervention(s) in this Clinical Trial

• Biological: rituximab
• Drug: cyclophosphamide
• Drug: methylprednisolone
• Drug: prednisone

Primary Measures

• Event-free survival at 2 years
  • Safety Issue?: 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: 30 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Children's Oncology Group

Overall Clinical Trial Officials and Contacts

Thomas G. Gross, MD, PhD Study Chair Nationwide Children's Hospital  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00066469

Study ID Number: CDR0000316241

ClinicalTrials.gov Identifier: NCT00066469

Health Authority: United States: Federal Government

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