Purified CD34+ Hematopoietic Stem Cell Transplantation From Alternate Donors for Patients With Severe Aplastic Anemia

Study Overview
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Brief Summary
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This study is for patients with Severe Aplastic Anemia (SAA). A stem cell transplant from a genetically matched sibling donor can help or cure this disease in 85 to 100 percent of patients. Stem cells are immature blood cells that grow to become red blood cells, white blood cells or platelets. A genetic match means a brother or sister has same immune type (HLA type) as the patient. Unfortunately, few patients have a matched sibling donor. The chance of negative outcomes is much higher with other types of donors. This study will test the success of a new approach to stem cell transplant for SAA. Patients in this study will receive drugs and radiation treatment to destroy their diseased bone marrow and to prepare them for stem cell transplant. Bone marrow is the tissue inside the bones where stem cells are made.Stem cells will be harvested from the blood or bone marrow of genetically matched unrelated donors or partially matched family donors. The stem cells will be filtered using a new device that is currently under study. The patients will receive large doses of the filtered stem cells (stem cell graft). Researchers want to find out how the study treatment affects patients, the disease, and the chances for survival.

Conditions
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Aplastic Anemia

Intervention / Treatment
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* Procedure: Allogeneic stem cell transplant
* Drug: Fludarabine, Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age < 21 years Diagnosis of severe aplastic anemia. (As defined by at least 2 of the following: ANC < 500/μl, platelet count < 20,000/μl, and a reticulocyte count < 1% after correction for the hematocrit. In addition, the diagnostic bone marrow biopsy must contain less than 25% of the normal cellularity). Patient must have failed one or more courses of immunosuppressive therapy that included ATG. As immunosuppression may take up to 6 months to demonstrate a response, patients must have been observed to have failed immunosuppression for a minimum of six months. Absence of suitable HLA-matched sibling donor. Negative serum pregnancy test for females with child bearing potential. Patient/parent/guardian is able to provide informed consent. Exclusion Criteria: Patients with a life expectancy < 6 weeks. Patients with severe renal disease (creatinine clearance < 40cc/min/1.73m2) Patients with pre-existing severe restrictive pulmonary disease (FVC <40% of predicted)

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Procedure: Allogeneic stem cell transplant|nan|
|Drug: Fludarabine, Cyclophosphamide|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To learn the safety of stem cell transplantation in patients with unrelated donors or partially matched family donors |  |  | 
| To study the effects (good and bad) of this treatment on the patients, the aplastic anemia, and survival |  |  | 
| To learn how well the donor bone marrow grows in patients who receive the research treatment |  |  | 
| To learn how many patients need extra T-cells or extra stem cells from the donor to help the donor's blood stem cells grow |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aplastic Anemia