Reduced Intensity Conditioning for Umbilical Cord Blood Transplant in Pediatric Patients With Non-Malignant Disorders
Condition: Non Malignant Disorders; Immunodeficiencies; Congenital Marrow Failures; Hemoglobinopathies; Inborn Errors of Metabolism; Sickle Cell; Thalassemia; Lysosomal Storage Disease
MeSH terms: Thalassemia; Hemoglobinopathies; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Immunologic Deficiency Syndromes
Intervention: Unrelated Umbilical Cord Blood Transplant; Reduced Intensity Conditioning
Intervention description: Reduced Intensity Conditioning for unrelated umbilical cord blood transplant
Intervention MeSH terms: Fludarabine; Melphalan; Thiotepa; Hydroxyurea
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Maximum age: 21 Years
Healthy volunteers: No
Keywords: Immunodeficiencies; Congenital Marrow Failures; Hemoglobinopathies; Inborn Errors of Metabolism; SCIDS; Wiskott Aldrich; FEL; HLH; IPEX; LAD; Sickle Cell; Thalassemia; Omenn's Syndrome; Hurler's Syndrome; MLD; ALD; Sanfilippo; Krabbe; Hunter's syndrome; TaySachs; Diamond Blackfan Anemia; transplant; MPS; Gaucher

Summary:

      The primary objective is to determine the feasibility of attaining acceptable rates of donor
      cell engraftment (>25% donor chimerism at 180 days) following reduced intensity conditioning
      (RIC) regimens in pediatric patients < 21 years receiving cord blood transplantation for
      non-malignant disorders.
    

Eligibility criteria:

        Inclusion Criteria:

          -  0-21 years of age with a diagnosis of a immunodeficiency, congenital marrow failure
             syndrome, inborn error of metabolism, or hereditary anemia

          -  Appropriately matched related or unrelated umbilical cord blood unit with a cell dose
             ≥ 3 x 10e7cells/kg

          -  Performance score (lansky or karnofsky) greater than or equal to 70

          -  Adequate organ function (Creatinine ≤ 2.0 mg/dl and creatinine clearance ≥ 50
             ml/min/1.73 m2; Hepatic transaminases (ALT/AST) ≤ 4 x normal; Shortening fraction >26%
             or ejection fraction >40% or > 80% of normal value for age; Pulmonary function tests
             demonstrating CVC or FEV1/FVC of >60% of predicted for age.)

          -  Informed consent

          -  Not pregnant or breast feeding

          -  Minimum life expectancy of at least 6 months

          -  HIV negative

          -  No uncontrolled infections at the time of cytoreduction

          -  Disease specific inclusion criteria

        Exclusion Criteria:

          -  Patients with hemoglobinopathies > 3 years of age

          -  UCB unit with a total nucleated cell count < 3 x 10e7/kg or > 2 antigen mismatching

          -  Available HLA-matched related living donor able to donate without previous UCB
             donation

          -  Allogeneic hematopoietic stem cell transplant within the previous 6 months

          -  Any active malignancy, MDS, or any history of malignancy

          -  Severe acquired aplastic anemia

          -  DLCO < 60% of normal value for age; requirement for supplemental oxygen

          -  Uncontrolled bacterial, viral or fungal infection (currently taking medication and
             progression of clinical symptoms)

          -  Pregnancy or nursing mother

          -  HIV/HTLV seropositive, Hep B surface antigen positive, or HCV RNA positive by PCR

          -  Any condition that precludes serial follow-up