HLA-haploidentical Hematopoietic Stem Cell Transplantation for Children and Adolescents With Acute Leukemia, Myelodysplastic Syndrome and Solid Tumors

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Conditioning with total body irradiation (TBI) and fludarabine, cyclophosphamide and anti-thymocyte globulin may induce the engraftment cross the immunologic barrier in the setting of HLA-haploidentical allogeneic hematopoietic cell transplantation. In addition, T-cell depletion may contribute to prevent developing severe acute graft versus host disease (GVHD) in haploidentical transplantation. PURPOSE: This phase I/II trial is to evaluate the safety and efficacy of TBI, fludarabine, cyclophosphamide and antithymocyte globulin with T-cell depleted graft from haploidentical donors in treating patients with acute leukemia and myelodysplastic syndrome.

Official Title
-----------------
HLA-haploidentical Allogeneic Hematopoietic Cell Transplantation Using CD3 Depletion for Children and Adolescents With Acute Leukemia, Myelodysplastic Syndrome and Solid Tumors After Conditioning of TBI, Fludarabine, Cyclophosphamide and Antithymocyte Globulin

Conditions
-----------------
Acute Leukemia, Myelodysplastic Syndrome, Solid Tumors

Intervention / Treatment
-----------------
* Biological: anti-thymocyte globulin
* Biological: filgrastim
* Radiation: Total body irradiation
* Drug: Fludarabine
* Drug: cyclophosphamide
* Drug: Tacrolimus
* Drug: Mycophenolate mofetil
* Drug: Rituximab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Disease characteristics Acute lymphoblastic leukemia (first remission, high risk; beyond first remission; refractory) Acute myeloblastic leukemia (first remission, high risk; beyond first remission; refractory) Myelodysplastic syndrome Solid tumors (Refractory/relapse) No HLA-identical family member or closely matched (8 or 7 of 8 HLA-locus match) unrelated marrow donor available HLA-haploidentical related donor available Exclusion criteria Active fungal infections HIV positive Pregnant or nursing

Ages Eligible for Study
-----------------
Maximum Age: 21 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HAPLO<br> | Biological: anti-thymocyte globulin<br>* On days -10 to -9<br>Biological: filgrastim<br>* Beginning on day 4 and continuing until blood counts recover<br>Radiation: Total body irradiation<br>* 2Gy D-6 to D-4<br>Drug: Fludarabine<br>* 30mg/M2 once daily IV on days -8 to -4<br>Drug: cyclophosphamide<br>* 60 mg/kg IV on day-3 and -2<br>Drug: Tacrolimus<br>* begin on 0<br>Drug: Mycophenolate mofetil<br>* begin on 0<br>Drug: Rituximab<br>* 375mg/m2 on day +21<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transplantation-related mortality and overall survival of TBI, Fludarabine, Cyclophosphamide and anti-thymocyte globulin for engraftment of CD3 depleted haploidentical peripheral blood stem cells. |  | 2 years post-transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Engraftment and graft failure rates | Number of patients who failed to stable engraftment by 28 days | 28 days engraftment and graft failure | 
| Incidence of acute GVHD | Number of patients with acute GVHD. | 100 days post-transplant | 
| Treatment related mortality | Number of death after transplantation | 100 days post-transplant | 
| Relapse rate and overall survival |  | 2 year after transplantation | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
TBI, Fludarabine, CD3 depletion, Children and adolescents, Haploidentical hematopoietic stem cell transplantation