Reduced Intensity Transplant Conditioning Regimen for Severe Thalassemia

Study Overview
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Brief Summary
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This study is being done to determine if blood cell transplants, with either bone marrow or cord blood from unrelated donors, are effective in children with severe thalassemia and if this treatment approach has acceptable risks and side effects. This study includes a preparative regimen with Hydroxyurea, Alemtuzumab, Fludarabine, Thiotepa and Melphalan that provides intense host immunosuppression without myeloablation. The primary hypothesis is that this regimen will promote stable engraftment of unrelated donor hematopoietic cells, support normal erythropoiesis, and result in an event free survival of > 75% of children with thalassemia major.

Official Title
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A Pilot Trial of Unrelated Donor Hematopoietic Cell Transplantation for Children With Severe Thalassemia Using a Reduced Intensity Conditioning Regimen (The URTH Trial)

Conditions
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Severe Thalassemia

Intervention / Treatment
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* Drug: Transplant conditioning regimen of alemtuzumab, fludarabine, and melphalan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1-16.00 years old Have transfusion dependent thalassemia major Shall not have an HLA-matched family donor Must have a suitably matched unrelated marrow donor or UCB product Lansky score >/= 70 Adequate pulmonary, renal, liver, and other organ function as defined in protocol Negative pregnancy test Adequate total nucleated cell or CD34+ dose of product as defined in protocol Iron chelation must be discontinued >/= 48 hours prior to conditioning regimen Exclusion Criteria: Pregnant or breastfeeding HIV positive Prior allogeneic marrow or stem cell transplantation

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum 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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Conditioning regimen<br>Hydroxyurea days -50 to -21 Alemtuzumab days -21 to -19 Fludarabine days -8 to -4 Thiotepa day -4 Melphalan day -3 Stem cell infusion day 0 | Drug: Transplant conditioning regimen of alemtuzumab, fludarabine, and melphalan<br>* Days -50 to -21: Hydroxyurea 30mg/kg po Day -22: Alemtuzumab 3mg IV Day -21: Alemtuzumab 10mg IV Day -20: Alemtuzumab 15mg IV Day -19: Alemtuzumab 20mg IV Day -8: Fludarabine 30mg/m2 IV Day -7: Fludarabine 30mg/m2 IV Day -6: Fludarabine 30mg/m2 IV Day -5: Fludarabine 30mg/m2 IV Day -4: Fludarabine 30mg/m2 IV Day -4: Thiotepa 8mg/kg IV Day -3: Melphalan 140mg/m2 IV Day 0: Stem cell infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Objective: Event-free Survival at 1 Year. |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of Graft Versus Host Disease (GVHD) |  | 2 years | 
| Median Time to ANC Engraftment |  | 100 days | 
| Median Time to Platelet Engraftment |  | 100 days | 
| Incidence of Disease Recurrence |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thalassemia, Alemtuzumab, Hematopoietic cell transplant, non-myeloablative