Stem Cell Transplantation for Sickle Cell Anemia
Condition: Sickle Cell Disease
MeSH terms: Anemia, Sickle Cell
Study type: Interventional
Phase: Phase 3

Summary: 
      This protocol will be investigating the use of stem cell transplantation, in related donors,
      to cure sickle cell disease. Sickle cell disease is a recessive disorder caused by a point
      mutation that results in the substitution of valine for glutamic acid at the sixth position
      in the B-chain of hemoglobin. This leads to sickling of the red blood cells under many
      conditions, such as hypoxia, dehydration, and hyperthermia. The sickling leads to
      vaso-occlusion, which causes irreversible damage in almost all systems in the body, including
      the central nervous system (CNS), lungs, heart, bones, eyes, liver, and kidneys.
    

Detailed description: 
      Primary objective:

      1) To determine disease free survival (DFS) at two years after matched sibling transplant
      using bone marrow (BM) after a conditioning regimen consisting of distal timed Alemtuzumab,
      Fludarabine, and Melphalan for patients 2-30 y/o

      Secondary objectives:

        1. Overall survival

        2. Rate of neutrophil and platelet engraftment for BM

        3. Incidence of graft failure

        4. Incidence of grade II-IV and grade III-IV acute graft vs host disease (GVHD)

        5. Incidence of chronic GVHD

        6. Incidence of other transplant complications, such as veno-occlusive disease, central
           nervous system (CNS) toxicity, and idiopathic pneumonia syndrome (IPS)

        7. Incidence of reactivation of CMV, EBV, adenovirus, BK/JC virus

        8. Incidence of invasive fungal disease

        9. Time to immune reconstitution via monitoring of lymphocyte subpopulations and
           immunoglobulin levels
    

Intervention name(s): Alemtuzumab; Fludarabine; Melphalan; Stem Cells
Intervention type(s): Drug; Drug; Drug; Procedure
Intervention description(s): Adjusted Ideal Body Weight Formula: AIBW = IBW + [(0.4) x (ABW - IBW)]
b) Medications
i.) Alemtuzumab I. Hb S% must be < or = 45% within 7 days prior to initiation of Alemtuzumab II. Iron chelation and hydroxyurea must be discontinued >48 hours before initiating therapy III. Alemtuzumab will be diluted in 100mL of 0.9% NS and infused at a rate as below; I. Fludarabine should be diluted in 100 ml 0.9%NS and given over 30 minutes. II. A daily dose of an antiemetic should be given 30 minutes prior to administration of the Fludarabine; I. Melphalan should be diluted in 0.9%NS to a concentration of 0.1 -0.45 mg/mL and given over 45 minutes. *Entire dose must be infused within 60 minutes of reconstitution in Pharmacy.
II. A daily dose of an antiemetic should be given 30 minutes prior to administration of the Melphalan III. Patients should be encouraged to suck on a popsicle or something similar during the Melphalan infusion.; Infusion of Hematopoietic Stem Cells
Other intervention name(s): Alemtuzumab (Campath); Fludarabine (Fludara); Melphalan (Alkeran)
Intervention MeSH terms: Fludarabine; Fludarabine phosphate; Melphalan; Alemtuzumab
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Stem cell transplant; Sickle cell; Stem cell transplantation; Related; Unrelated