Non-Myeloablative Bone Marrow Transplant for Patients With Sickle Cell Anemia and Other Blood Disorders
Condition: Sickle Cell Disease
MeSH terms: Anemia, Sickle Cell
Intervention: Cyclophosphamide; Fludarabine; Mycophenolate mofetil; Sirolimus; Allogeneic bone marrow transplant; Total body irradiation - 200; Levetiracetam; Anti-thymocyte globulin; Total body irradiation - 400
Intervention description: Cyclophosphamide (Cy) 14.5 mg/kg/day intravenously (IV) on Days -6 and -5 and 50 mg/kg/day IV on Days +3 and +4.; Fludarabine 30 mg/m^2/day IV on Days -6, -5, -4, -3, and -2.; Mycophenolate mofetil 15 mg/kg by mouth (PO) three times a day from Day +5 to Day +35.; The first dose of Sirolimus is 6 mg PO on Day +5. Further dosing is adjusted according to drug levels. Sirolimus is continued through Day +365.; An allogeneic bone marrow transplant is a procedure that involves taking bone marrow from a donor and giving it to a recipient.; 200 centigray (cGy) in one fraction on Day -1.; Given at 500 mg PO twice daily from Day -6 to Day +365.; Test dose of 0.5 mg/kg IV given on Day -9, then 2 mg/kg/day IV on Day -8 and -7.; 400 centigray (cGy) in one fraction on Day -1.
Intervention MeSH terms: Mycophenolic Acid; Sirolimus; Cyclophosphamide; Fludarabine; Levetiracetam; Thymoglobulin; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 43.0
Sex: All
Minimum age: 2 Years
Maximum age: 70 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: sickle cell disease

Summary:

      RATIONALE: Giving low doses of chemotherapy, such as fludarabine and cyclophosphamide, and
      total-body irradiation before a donor bone marrow transplant helps stop the growth of
      abnormal cells. It also helps stop the patient's immune system from rejecting the donor's
      stem cells. When the healthy stem cells from a donor are infused into the patient they may
      help the patient's bone marrow make stem cells, red blood cells, white blood cells, and
      platelets. Sometimes the transplanted cells from a donor can make an immune response against
      the body's normal cells. Giving sirolimus and mycophenolate mofetil after transplant may stop
      this from happening.

      PURPOSE: This phase II trial is studying how well giving fludarabine and cyclophosphamide
      together with total-body irradiation followed by a donor bone marrow transplant works in
      treating patients with sickle cell anemia and other blood disorders.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Diagnosis of 1 of the following sickle cell anemias (Hb SS):

               -  Hb S/β° thalassemia

               -  Hb S/β+ thalassemia

               -  Hb SC disease

               -  Hb SE disease

               -  Hb SD disease

               -  Hemoglobin SO-Arab disease

               -  Hb S/hereditary persistence of fetal hemoglobin

          -  Meets 1 of the following criteria:

               -  History of invasive pneumococcal disease

               -  Stroke or CNS event lasting > 24 hours

               -  MRI changes indicative of brain parenchymal damage

               -  Evidence of cerebrovascular disease by magnetic resonance angiography

               -  Acute chest syndrome requiring exchange transfusion or hospitalization

               -  Recurrent vaso-occlusive pain crisis (> 2 per year for the last 2 years)

               -  Stage I or II sickle lung disease

               -  Sickle retinopathy

               -  Osteonecrosis

               -  Red cell alloimmunization (> 2 antibodies) during long-term transfusion

               -  Constellation of dactylitis in the first year of life AND a baseline hemoglobin <
                  7 g/dL and leukocytosis (WBC > 13.4/mm^3) in the absence of infection during the
                  second year of life

               -  Pitted RBC count > 3.5% during the first year of life

          -  Ineligible for or refused bone marrow transplantation from an HLA-matched sibling
             donor

          -  Partially mismatched (at least haploidentical) first-degree relative donor available

               -  No minor (donor anti-recipient) ABO incompatibility if an ABO compatible donor is
                  available

        PATIENT CHARACTERISTICS:

          -  ECOG performance status (PS) 0-1 OR Karnofsky or Lansky PS 70-100%

          -  LVEF ≥ 35%

          -  FEV_1 and forced vital capacity ≥ 40% predicted

          -  Direct bilirubin < 3.1 mg/dL

          -  No moderate to severe pulmonary hypertension by ECHO

          -  No debilitating medical or psychiatric illness that would preclude study participation

          -  No HIV positivity

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

        PRIOR CONCURRENT THERAPY:

          -  No prior transfusions from donor

          -  No immunosuppressive agents, including steroids as antiemetics, within 24 hours after
             the last dose of post-transplantation cyclophosphamide