Allogeneic Stem Cell Transplant for Patients With Severe Aplastic Anemia
Patients have been diagnosed with severe Aplastic Anemia that have not responded to treatment with immunosuppressive therapy (drugs that suppress the immune system, for example Steroids). The immune system is the system in the body that helps protect the body and fights bacterial, viral and fungal infections.
Research studies have shown that patients with Aplastic Anemia have improved survival (may live longer) after receiving a HLA (Human Leukocyte Antigen) identical sibling (brother and sister) stem cell transplants. Patients who do not have matched siblings can undergo immunosuppressive therapy, which has also shown to improve outcome. Unfortunately patients who do not respond to immunosuppressive therapy usually die. The best chance of survival for these patients is an HLA matched unrelated or mismatched related stem cell transplant as described below.
Stem cells are created in the bone marrow. They mature into different types of blood cells that people need including red blood cells which carry oxygen around the body, white blood cells which help fight infections, and platelets which help the blood to clot and prevent bleeding. For a matched unrelated stem cell transplant, stem cells are collected from a person (donor) who is not related to the patient but who has the same type of stem cells. For a mismatched related stem cell transplant, stem cells are collected from a donor who is related to the patient and whose stem cells are almost the same as those of the patient but not exactly. The patient then receives high dose chemotherapy. This chemotherapy kills the stem cells in the patient's bone marrow. Stem cells that have been collected from the donor are then given to the patient to replace the stem cells that have been killed.
The major problems associated with these types of stem cell transplants are graft rejection (where the patient's immune system rejects the donor stem cells) and severe graft versus host disease (GVHD), where the donors stem cell reacts against the patient's tissues in the body.
Radiation: Total Body Irradiation (TBI)
Procedure: Stem cell infusion
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Allogeneic Stem Cell Transplantation for Patients With Severe Aplastic Anemia, Using Matched Unrelated Donors and Mismatched Related Donors (SAA MUD)|
- Number of Subjects Alive at 100 Days Post Transplant [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
- Number of Patients With Engraftment Rate at 100 Days Post Transplant [ Time Frame: 100 days post transplant ] [ Designated as safety issue: Yes ]Absolute neutrophil count greater than 0.5 X 109/ml for at least 3 days
- Number of Patients With Acute GVHD at 100 Days Post Transplant [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
- Number of Patients With Chronic GVHD at 2 Years Post Transplant [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- Number of Subjects Alive at 1 Year Post Transplant [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
- Number of Subjects Alive at 2 Years Post Transplant [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
|Study Start Date:||February 2002|
|Study Completion Date:||July 2012|
|Primary Completion Date:||July 2012 (Final data collection date for primary outcome measure)|
Patients with a diagnosis of severe aplastic anemia who require an allogeneic stem cell transplant but lack an Human Leukocyte Antigen (HLA) identical family member.
Cytoxan, Campath, TBI-Total Body Irradiation, FK-506, Methotrexate, Stem Cell Infusion
Cytoxan will be given at 50 mg/kg per dose for 4 successive days.
Other Name: CyclophosphamideDrug: Campath
Campath will be given at a dose of 3 mg for patients whose weight is between 5 and 15 kg; at a dose of 5 mg for patients whose weight is between 16 and 30 kg; and at a dose of 10 mg for patients whose weight is greater than 30 kg. The last dose of Campath should be 24 hours or more before stem cell infusion.
Other Name: alemtuzumabRadiation: Total Body Irradiation (TBI)
TBI will be given at a dose of 200 cGy for 6/6 HLA match and at a dose of 400 cGy in two fractions of 200 cGy each for 5/6 HLA matched donor.
Other Name: IrradiationDrug: FK-506
FK-506 will be given at a dose of 0.03 mg/kg/day via continuous infusion over 24 hours from 4pm on day -2 until engraftment or when patient is able to take by mouth (PO), then 0.03 mg/kg PO every 12 hours.
Other Name: TacrolimusDrug: Methotrexate
Methotrexate will be administered on day +1, day +3, day +6 and day +11 at a dose of 5 mg/m2. The day +11 dose may be omitted at the discretion of the bone marrow transplant (BMT) in-patient attending physician.Procedure: Stem cell infusion
Where possible patients will receive bone marrow. Marrow will be collected as per National Marrow Donor Program (NMDP) guidelines to provide a volume of 15-20 ml/kg of marrow and/or 2-4 X 10^8 nucleated cells/kg. In case marrow cannot be collected, peripheral blood stem cell (PBSC) will be substituted. A minimum of 5-6 X 10^6 CD 34+ cells/kg should be collected, with a target of 10 X 10^6/kg.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00578903
|United States, Texas|
|Texas Children's Hospital|
|Houston, Texas, United States, 77030|
|The Methodist Hospital|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Kathryn Leung, MD||Baylor College of Medicine|