Human Leukocyte Antigen (HLA)-Haploidentical Hematopoietic Stem Cell Transplantation for Patients With Aplastic Anemia

Study Overview
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Brief Summary
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Rationale: Chemotherapy with 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, depletion CD3±CD19 cells 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 fludarabine, cyclophosphamide and antithymocyte globulin with CD3±CD19 depleted graft from haploidentical donors in treating patients with aplastic anemia.

Official Title
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HLA-haploidentical Allogeneic Hematopoietic Cell Transplantation Using CD3±CD19 Depletion for Patients With Aplastic Anemia After Conditioning of Fludarabine, Cyclophosphamide and Antithymocyte Globulin

Conditions
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Aplastic Anemia

Intervention / Treatment
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* Biological: anti-thymocyte globulin
* Biological: filgrastim
* Drug: Fludarabine
* Drug: Cyclophosphamide
* Procedure: CD3±CD19 depleted hematopoietic stem 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
Allocation: Non-Randomized
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 -3 to -1<br>Biological: filgrastim<br>* Beginning on day 4 and continuing until blood counts recover<br>Drug: Fludarabine<br>* 30mg/M2 once daily IV on days -6 to -2<br>Drug: Cyclophosphamide<br>* 60 mg/kg IV on day-3 and -2<br>Procedure: CD3±CD19 depleted hematopoietic stem 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 the engraftment rate and survival of CD3±CD19 depleted haploidentical peripheral blood stem cell transplantation after conditioning with fludarabine, cyclophosphamide and anti-thymocyte globulin. |  | 2 years post-transplant | 

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 post-transplant | 
| To estimate the risk of acute GVHD | Number of patients with acute GVHD. | 100 days post-transplant | 
| To assess treatment related mortality | Number of death after transplantation | 100 days post-transplant | 
| To estimate overall survival |  | 1 year after transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aplastic anemia, Fludarabine, CD3±CD19 depletion, Haploidentical hematopoietic stem cell transplantation