Hematopoietic Stem Cell Transplant for High Risk Hemoglobinopathies

Study Overview
=================
Brief Summary
-----------------
This is a study to collect the outcomes of stem cell transplantation for patients with hematologic diseases other than cancer.

Official Title
-----------------
MT2014-10C: Allogeneic Hematopoietic Stem Cell Transplant for Patients With High Risk Hemoglobinopathies and Other Red Cell Transfusion Dependent Disorders

Conditions
-----------------
Sickle Cell Disease, Transfusion Dependent Alpha- or Beta- Thalassemia, Diamond Blackfan Anemia, Paroxysmal Nocturnal Hemoglobinuria, Glanzmann Thrombasthenia, Severe Congenital Neutropenia, Shwachman-Diamond Syndrome, Non-Malignant Hematologic Disorders

Intervention / Treatment
-----------------
* Drug: Reduced Toxicity Ablative Regimen
* Drug: Reduced Intensity Preparative Regimen
* Drug: Myeloablative Preparative Regimen


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of Sickle Cell Disease, Thalassemia, Diamond Blackfan Anemia or other non-malignant hematologic disorders for which a stem cell transplant is indicated Acceptable stem cell source identified Performance status of ≥ 70% (Karnofsky),or ≥ 70 (Lansky play score) Creatinine <2.0 mg/dl for adults or glomerular filtration rate > 50 ml/min for children Bilirubin, Aspartate Aminotransferase, Alkaline phosphatase <5 times the upper limit of institutional normal Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction > 40% Exclusion Criteria: active, uncontrolled infection pregnant or breastfeeding HIV positive

Ages Eligible for Study
-----------------
Maximum Age: 55 Years

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Reduced Toxicity Ablative Regimen<br>For use in patients with a matched sibling donor or unrelated UCB donor and DBA patients who are <12 years and/or have mild/moderate iron exposure. | Drug: Reduced Toxicity Ablative Regimen<br>* Anti-thymocyte Globulin (ATG) Fludarabine Busulfan Stem Cell Infusion Day 0<br>|
| Experimental: Reduced Intensity Preparative Regimen<br>For use in patients with unrelated donor bone marrow and for DBA patients who are >12 years and/or have significant iron exposure. | Drug: Reduced Intensity Preparative Regimen<br>* Alemtuzumab Cyclophosphamide Fludarabine Total Body Irradiation (TBI) Stem Cell Infusion Day 0<br>|
| Experimental: Myeloablative Preparative Regimen<br>For use in patients with a matched sibling donor, unrelated umbilical cord blood and in those with severe thalassemia. | Drug: Myeloablative Preparative Regimen<br>* Alemtuzumab Cyclophosphamide Busulfan Stem Cell Infusion Day 0<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of graft failure |  | 42 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival |  | 6 months, 1 and 2 years | 
| disease free survival | patient no longer needing red blood cell transfusion and/or a hemoglobin S level at that of the donor ( sickle cell disease only) | 6 months, 1 and 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Stem Cell Transplant