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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)

Phase 2
30 Years
Not Enrolling
Lymphoproliferative Disorder

Thank you

Trial Information

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)


- 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.

Inclusion Criteria


- 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

- Liver (coagulopathy, transaminitis, and/or hyperbilirubinemia)

- Lungs (interstitial pneumonitis with or without pleural

- 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



- Under 31

Performance status

- Not specified

Life expectancy

- NF-PTLD patients:

- At least 8 weeks


- See Disease Characteristics


- See Disease Characteristics


- Not specified


- See Disease Characteristics


- Not pregnant or nursing

- Fertile patients must use effective contraception

- HIV negative


Biologic therapy

- More than 1 month since prior rituximab


- More than 4 weeks since prior chemotherapy and recovered

Endocrine therapy

- Not specified


- Not specified


- See Disease Characteristics

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Event-free survival at 2 years

Outcome Description:

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

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Thomas G. Gross, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Nationwide Children's Hospital


United States: Federal Government

Study ID:




Start Date:

April 2004

Completion Date:

Related Keywords:

  • Lymphoproliferative Disorder
  • post-transplant lymphoproliferative disorder
  • Lymphoproliferative Disorders



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