Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Cyclophosphamide, Rituximab, and Either Prednisone or Methylprednisolone in Treating Patients With Lymphoproliferative Disease After Solid Organ Transplantation

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	Under 31	NCI	COG-ANHL0221 NCT00066469, ANHL0221

Objectives

1. 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.
2. 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.
3. Determine the response rate in patients treated with this regimen.
4. Determine the PTLD gene expression profile by microarray analysis and fluorescent in situ hybridization in patients treated with this regimen.
5. Determine the accrual rate of patients to this study.

Entry 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

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

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

Expected Enrollment

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.

Outcomes

Event-free survival at 2 years

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.

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Thomas Gross, MD, PhD, Protocol chair		Ph: 614-722-3552

Registry Information
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)
Trial Start Date		2004-04-19
Trial Completion Date		2008-07-03 (estimated)
Registered in ClinicalTrials.gov		NCT00066469
Date Submitted to PDQ		2003-06-18
Information Last Verified		2008-08-20
NCI Grant/Contract Number		CA98543