Sequential Treatment of CD20-positive Posttransplant Lymphoproliferative Disorder (PTLD)

Study Overview
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Brief Summary
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Post-transplantation lymphoproliferative disorder (PTLD) develops in one to ten per cent of transplant recipients and can be EBV-associated. To improve long-term efficacy after rituximab monotherapy and to avoid the toxicity of CHOP seen in first-line treatment, the investigators initiated an international multicentre phase II trial to test whether the subsequent application of rituximab and four courses of three-weekly CHOP would improve the outcome of patients with PTLD: PTLD-1, sequential treatment (ST).

Official Title
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Treatment of Patients With Posttransplant Lymphoproliferative Disorder (PTLD) With a Sequential Treatment Consisting of Anti-CD20 Antibody Rituximab and CHOP+GCSF Chemotherapy (Including 1st+2nd Amendment)

Conditions
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Post-transplantation Lymphoproliferative Disorder

Intervention / Treatment
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* Drug: Rituximab
* Drug: CHOP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: PTLD with or without EBV association, confirmed after biopsy or resection Measurable disease of > 2 cm in diameter and/or bone marrow involvement Patients having undergone heart, lung, liver, kidney, pancreas, small intestine transplantation or other or a combination of the organ transplantations mentioned Karnofsky scale >50% or ECOG ≤ 3 Reduction of immunosuppression with or without antiviral therapy A complete surgical extirpation of tumor was not performed A radiation therapy was not performed Effective contraception for women in childbearing age Patient's written informed consent and written consent for data collection Patients are > 18 years (or ≥ 15 years with parental agreement ) Exclusion Criteria: Life expectancy less than 6 weeks Karnofsky-scale <50% or ECOG =3 Treatment with rituximab before Known allergic reactions against foreign proteins Concomitant diseases, which exclude the administration of therapy as outlined by the study protocol non-compensated heart failure Dilatative cardiomyopathy Myocardial infarction during the last 6 months Severe non-compensated hypertension Severe non-compensated diabetes mellitus Renal insufficiency (creatinine more than 3-fold of the upper normal value), not related to lymphoma. Hepatic insufficiency with transaminase values greater than 3-fold of the normal values and/or bilirubin levels >3.0 mg/dl, not related to lymphoma Clinical signs of cerebral dysfunction Women during the lactation period, pregnant or of childbearing potential not using a reliable contraceptive method Involvement of the central nervous system by the disease Severe psychiatric disease Known to be HIV positive Missing written informed consent of the patient

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Rituximab|Rituximab 375 mg/m2 IV on days 1, 8, 15 and 22.|
|Drug: CHOP|Cyclophosphamide 750 mg/m2 IV, adriamycine 50 mg/m2 IV, vincristine 1.4mg/m2 IV, and prednisone 50mg/m2 PO every 3 weeks at days 50, 72, 94 and 116.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of patients with complete and partial remission |  | 1 month (plus or minus 7 days) after the last cycle of chemotherapy | 
| response duration |  | from date of best response until the date of first documented progression, assessed up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of patients with treatment-related death |  | from start of treatment, assessed up to 12 months after the end of treatment | 
| overall survival |  | from start of treatment until date of death from any cause, assessed up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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1st-line therapy, single agent rituximab, CHOP, PTLD