Haploidentical Stem Cell Transplantation for Children With Acquired Severe Aplastic Anemia

Study Overview
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Brief Summary
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Rationale: Fludarabine, cyclophosphamide, anti-thymocyte globulin and low-dose total body irradiation (LD-TBI) may induce the engraftment cross the immunologic barrier in the setting of HLA-haploidentical allogeneic hematopoietic cell transplantation. In addition, depletion of CD3 cells may contribute to prevent developing severe acute graft versus host disease (GVHD) in haploidentical transplantation. Purpose: Phase II trials to evaluate the efficacy of haploidentical stem cell transplantation with fixed dose of T cells after in vitro T cell depletion using CD3 monoclonal antibody for children with acquired severe aplastic anemia

Official Title
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Haploidentical Stem Cell Transplantation With Fixed Dose of T Cells After in Vitro T Cell Depletion Using CD3 Monoclonal Antibody for Children With Acquired Severe Aplastic Anemia

Conditions
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Acquired Aplastic Anemia

Intervention / Treatment
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* Drug: Fludarabine
* Drug: Cyclophosphamide
* Biological: anti-thymocyte globulin
* Biological: filgrastim
* Radiation: Total body irradiation
* Procedure: CD3-depleted hematopoietic cell transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of life-threatening marrow failure (severe aplastic anemia) of nonmalignant etiology meeting 2 of the following criteria: Granulocyte count < 500/mm3, Corrected reticulocyte count < 1%, Platelet count < 20,000/mm3 No HLA-identical family member or closely matched (8 of 8 HLA-locus match) unrelated marrow donor available HLA-haploidentical related donor available Exclusion Criteria: Paroxysmal nocturnal hemoglobinuria or Fanconi anemia Clonal cytogenetic abnormalities or myelodysplastic syndromes Active fungal infections HIV positive Severe disease other than aplastic anemia that would severely limit the probability of survival during the graft procedure Pregnant or nursing

Ages Eligible for Study
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Maximum Age: 21 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: HAPLO<br> | Drug: Fludarabine<br>* 40mg/M2 once daily IV on days -7 to -4<br>Drug: Cyclophosphamide<br>* 60 mg/kg IV on day-3 and -2<br>Biological: anti-thymocyte globulin<br> <br> Biological: filgrastim<br> <br> * Other names: Beginning on day 4 and continuing until blood counts recover;Radiation: Total body irradiation<br>* 200 cGy per day on D-5 & -4<br>Procedure: CD3-depleted hematopoietic cell transplantation<br>* Immunogenetic depletion on CliniMACS<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess engraftment rate and survival of haploidentical stem cell transplantation with fixed dose of T cells after in vitro T cell depletion using CD3 monoclonal antibody for children with acquired severe aplastic anemia |  | 2 years posttransplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess engraftment and graft failure | Number of patients who failed to engraft by 28 days | 28 days posttransplant | 
| To estimate the risk of acute GVHD | Number of patients with acute GVHD. | 100 days posttransplant | 
| To assess treatment related mortality | Number of death after transplantation | 100 days posttransplant | 
| To estimate overall survival and failure free survival |  | 1 year posttransplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD3 depletion, Haploidentical hematopoietic stem cell transplantation, Aplastic anemia, T cell dose