Fludarabine, Cyclophosphamide, Doxorubicin and Rituximab for the Treatment of Post-transplant Lymphoproliferative Disease (PTLD)

Study Overview
=================
Brief Summary
-----------------
Fludarabine may be of benefit to prevent rejection of grafted solid organs in children during chemo-immunotherapy treatment for post transplant lymphoproliferative diseases (PTLDs).

Detailed Description
-----------------
Eligible to this study were patients less than 18 years old, presenting with non Burkitt, aggressive, CD20 positive PTLD, after solid organ transplants. Induction therapy consisted of two cycles of a combination of Fludarabine(30mg/sqm/day, days 1,2,3), Cyclophosphamide (750 mg/sqm/day, day 1), Doxorubicin (30 mg/sqm/day, day 1)and Rituximab (375 mg/sqm/day, day 4). Thereafter consolidation therapy was given as follows: two blocks for stage II or III with LDH less than 500 IU/L; three blocks for stage III with LDH >500 and < 1000 IU/L or stage IV with LDH < 1000 IU/L; four blocks for stage III or IV with LDH > 1000 IU/L. Blocks given were modified BFM blocks used for treatment of non Hodgkin B-lymphomas, as follows: Block 1: High Dose Methotrexate (HDMTX) 1.5 gr/sqm; Vincristine (VCR,1.5 mg/sqm); Cytarabine (from 120 to 150 mg/sqm x4); Ifosfamide (600 mg/sqm/day x5); VP-16 (80 mg/sqm/day x2); Dexamethasone (DXM,10 mg/sqm/day for 5 ays); Intrathecal Methotrexate-Cytarabine-Methylprednisolone(TIT). Block 2:HDMTX (3 gr/sqm); VCR (1.5 mg/sqm); Daunomycin (20 mg/sqm/day x2); Cyclophosphamide (160 mg/sqm/day x5); DXM (10 mg/sqm/day x5); TIT Block 3:Vindesine (3 mg/sqm); Cytarabine (3000 mg/sqm q 12 hours x4); VP-16 (100 mg/sqm q 12 hours x4); DXM (20 mg/sqm/day x5); Block 4 as Block 1. Outcome measures are: achievement of complete remission after induction therapy; incidence of infectious episodes; neurological toxicity; incidence of graft rejection; duration of complete remission.

Official Title
-----------------
Fludarabine, Cyclophosphamide, Doxorubicin and Rituximab for the Treatment of Post-transplant Lymphoproliferative Disease (PTLD)

Conditions
-----------------
Post-transplant Lymphoproliferative Disease (PTLD), Non Burkitt

Intervention / Treatment
-----------------
* Drug: fludarabine, cyclophosphamide, doxorubicin, rituximab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Children less 18 years old and Non Burkitt, CD20 positive aggressive PTLD and Solid organ transplant Exclusion Criteria: Burkitt PTLD

Ages Eligible for Study
-----------------
Minimum Age: 6 Months
Maximum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: chemotherapy<br> | Drug: fludarabine, cyclophosphamide, doxorubicin, rituximab<br>* Fludarabine i.v.(30 mg/sqm/day,day 1,2,3); Cyclophosphamide i.v.(750 mg/sqm, day 1); Doxorubicin i.v.(30 mg/sqm, day 1); Rituximab i.v. (375 mg/sqm, day 4).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission rate | No evidence of disease | 6 months | 
| graft rejection rate | preservation of normal organ function | 1 year after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Continuous complete remission rate | No evidence of disease | five years after the diagnosis |