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Allogeneic Stem Cell Transplant for Patients With Severe Aplastic Anemia (SAA) Using Matched Unrelated Donors and Mismatched Related Donors - NCT00578903-77030B(Clinical Trial 196249)



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City:  Houston
State:  
TX
Zip Code: 77030
Conditions: Aplastic Anemia
Purpose: Research studies have shown that patients with severe aplastic anemia (SAA) may live longer after receiving a HLA (human leukocyte antigen) identical sibling (brother and sister) stem cell transplant. 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. 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 donor's stem cells react against the patient's tissues in the body. The investigators want to see if adding CAMPATH 1H to the transplant medications helps improve the outcome of treating SAA with a stem cell transplant. Campath 1H is a special type of protein called an antibody, that works against certain types of blood cells. Campath 1H is important because it stays active in the body for a long time after infusion, which means it may work longer at preventing GVHD symptoms.
Study summary: Severe aplastic anemia (SAA) is a rare but serious disorder in children. Bone marrow transplant (BMT) with an HLA identical sibling is currently the treatment of choice for a child with SAA, as it offers a cure by restoration of normal hematopoiesis. The excellent results of marrow transplantation in children with HLA identical siblings and the low mortality and morbidity make transplantation the treatment of choice in young patients. Rejection is likely to be caused by allosensitization of the recipient to minor histocompatibility antigens through the transfusion of red cells and platelets. As a result, it is recommended that transfusions be avoided as much as possible in patients with aplastic anemia who are being considered for BMT, and always those from the transplant donor. The addition of antithymocyte globulin (ATG) to the cyclophosphamide preparative regimen has also contributed to the lower risk of graft failure. The other complication besides graft rejection, which is a major cause of late mortality and morbidity both as an immediate, and a delayed consequence of allogeneic BMT is Graft versus host disease (GVHD). GVHD is mediated by donor lymphocytes and histoincompatibility is a major risk factor for GVHD. There is also a clear association between age and risk of GVHD independent of the degree of histoincompatibility. The increased risks of GVHD with age contribute to poor survival post transplant in older patients. Thus excellent survival and low morbidity make allogeneic transplant the treatment of choice for children and adolescents. Children with SAA who lack an HLA identical sibling donor need alternative therapy. Transplant from an unrelated donor is a potentially curative alternative in patients who fail immunosuppressive therapy. An unrelated marrow search is initiated usually at the time of starting the immunosuppressive therapy to save time if transplant becomes necessary. Antithymocyte globulin (ATG) has been used with conventional conditioning to enhance depletion of the host's immune system with the intent of accelerating engraftment and reducing the risk of rejection. Similarly, CAMPATH-I is a rat antibody that recognizes the CD52 cell surface marker. CAMPATH-1H is a humanized antilymphocyte monoclonal antibody. The Campath-1 antigen in humans (CD52) is predominantly expressed on peripheral blood lymphocytes, monocytes, and macrophages. CAMPATH-1H causes lysis of lymphocytes by fixing to CD52, a highly expressed, non-modulating antigen on the surface of lymphocytes. It mediates the lysis of lymphocytes via complement and antibody dependent cell mediated cytotoxicity mechanisms. Extensive clinical data on the use of CAMPATH in stem cell transplant is available. To date, antibodies of the Campath series have been used in over 2000 bone marrow transplants primarily for the prevention of GVHD but also for reduction of graft rejection.
Criteria: Inclusion Criteria: 1. Diagnosis of Severe Aplastic Anemia (SAA) based on bone marrow aspirate and biopsy results. 2. Failure to respond to immunosuppressive therapy. 3. Lack of an Human Leukocyte Antigen (HLA) identical family member. 4. A 6/6 or 5/6 HLA matched unrelated donor or a 5/6 matched related donor available after high resolution HLA typing. 5. Age from birth to 60 years. Exclusion Criteria: 1. Severe disease other than aplastic anemia that would limit the probability of survival during the graft procedure. Patients who present with active infection must be treated to maximally resolve this problem before beginning the conditioning regimen. 2. Human immunodeficiency virus (HIV) seropositive patients 3. Patients who have clonal cytogenetic abnormalities or a myelodysplastic syndrome. 4. Patient greater than 60 years of age. 5. Women who are pregnant or nursing. 6. Patients with active hepatitis 7. Patients with severe cardiac dysfunction defined as shortening fraction < 25%. 8. Patients with severe renal dysfunction defined as creatinine clearance < 40 ml/mim/1.73m2. 9. Patient with severe pulmonary dysfunction with forced expiratory volume in the first second (FEV1), forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO) 40% of predicted or 3 standard deviations (SD) below normal.
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Data Source: ClinicalTrials.gov
Date Processed: April 13, 2010
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