Alemtuzumab, Fludarabine, and Busulfan Followed By Donor Stem Cell Transplant in Treating Young Patients With Hematologic Disorders
Condition: Congenital Amegakaryocytic Thrombocytopenia; Diamond-blackfan Anemia; Leukemia; Myelodysplastic Syndromes; Severe Congenital Neutropenia
MeSH terms: Leukemia; Preleukemia; Myelodysplastic Syndromes; Thrombocytopenia; Neutropenia; Anemia, Diamond-Blackfan; Syndrome
Intervention: alemtuzumab; busulfan; cyclosporine; fludarabine phosphate; methotrexate; methylprednisolone; allogeneic bone marrow transplantation; allogeneic hematopoietic stem cell transplantation; peripheral blood stem cell transplantation; umbilical cord blood transplantation
Intervention MeSH terms: Cyclosporine; Methylprednisolone; Methotrexate; Fludarabine phosphate; Fludarabine; Busulfan; Alemtuzumab; Cyclosporins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 35.0
Sex: All
Maximum age: 21 Years
Healthy volunteers: No
Keywords: de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; childhood acute myeloid leukemia in remission; childhood chronic myelogenous leukemia; congenital amegakaryocytic thrombocytopenia; Diamond-Blackfan anemia; severe congenital neutropenia; secondary acute myeloid leukemia; chronic phase chronic myelogenous leukemia; childhood myelodysplastic syndromes

Summary:

      RATIONALE: Monoclonal antibodies, such as alemtuzumab, can block cancer growth in different
      ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and
      help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such
      as fludarabine and busulfan, work in different ways to stop the growth of cancer cells,
      either by killing the cells or by stopping them from dividing. A peripheral stem cell, bone
      marrow , or umbilical cord blood transplant may be able to replace blood-forming cells that
      were destroyed by chemotherapy. Sometimes the transplanted cells from a donor can make an
      immune response against the body's normal cells. Giving cyclosporine together with
      methotrexate and methylprednisolone may stop this from happening.

      PURPOSE: This phase II trial is studying how well giving alemtuzumab together with
      fludarabine and busulfan works when given before donor stem cell transplant in treating young
      patients with hematologic disorders.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Diagnosis of 1 of the following hematologic conditions:

               -  Aplastic anemia with marrow aplasia, meeting all of the following criteria:

                    -  Absolute neutrophil count < 500/mm^3

                    -  Platelet and/or red cell transfusion dependent

               -  Chronic aplastic anemia, meeting all of the following criteria:

                    -  Transfusion dependent

                    -  Unresponsive to immunosuppressive therapy

                    -  Alternative matched unrelated donor has been identified

               -  Congenital marrow failure syndrome, including any of the following (with closely
                  matched related or unrelated donor):

                    -  Primary red cell aplasia (Diamond-Blackfan syndrome)

                    -  Congenital neutropenia (Kostmann's syndrome)

                    -  Amegakaryocytic thrombocytopenia

                    -  Congenital dyserythropoietic anemias

                    -  Other severe acquired cytopenias in which a transplantation using a combined
                       busulfan/cyclophosphamide conditioning regimen is indicated

               -  Hemoglobinopathy (with closely matched related or unrelated donor)

                    -  β-thalassemia major

                    -  Sickle cell anemia

                    -  Hemoglobin E/β-thalassemia

               -  Severe immunodeficiency disease

                    -  Chediak-Higashi disease

                    -  Wiskott-Aldrich syndrome

                    -  Combined immunodeficiency disease (Nezelof's)

                    -  Hyper immunoglobulin M (IgM) syndrome

                    -  Bare lymphocyte syndrome

                    -  Chronic granulomatous disease

                    -  Familial erythrohemophagocytic lymphohistiocytosis

               -  Other stem cell defects (e.g., osteopetrosis)

               -  Severe immune dysregulation/autoimmune disorders

                    -  Achieved a transient response to prior immunosuppressive therapy

               -  Chronic myelogenous leukemia

                    -  Disease in first chronic phase

               -  Acute myeloid leukemia

                    -  Disease in first remission

               -  Myelodysplastic syndromes

               -  Inborn errors of metabolism

               -  Histiocytosis

          -  No severe combined immunodeficiency disease

          -  Matched related or unrelated donor available by high resolution DNA typing

               -  Related donor, meeting both of the following criteria:

                    -  Matched at both human leukocyte antigen (HLA)-Drβ1 alleles

                    -  No more than 1 mismatch at the 4 HLA-A and -B alleles

               -  Unrelated donor, meeting 1 of the following criteria:

                    -  Marrow matched at both HLA-Drβ1 alleles AND no more than 1 mismatch at the 4
                       HLA-A and -B alleles

                    -  Umbilical cord blood matched at 5/6 HLA-A, -B, and -DRβ1 alleles with at
                       least 1 -DRβ1 match AND there are ≥ 3x10^5 CD34+ (Cluster of differentiation
                       34-positive) cells per kg body weight of recipient available at the time of
                       cryopreservation

        PATIENT CHARACTERISTICS:

          -  Cardiac ejection fraction ≥ 27%

          -  Creatinine clearance ≥ 50 mL/min by 24-hour urine collection or glomerular filtration
             rate

          -  DLCO (diffusion capacity of lung for carbon monoxide) ≥ 50% of predicted (corrected
             for anemia/lung volume)

        PRIOR CONCURRENT THERAPY:

          -  No prior transplantation for leukemia from which patient remains engrafted and
             alemtuzumab is not needed as part of the conditioning regimen