Transplantation for Patients With Sickle Cell Disease From Mismatched Family Donors of Bone Marrow
Condition: Sickle Cell Disease
MeSH terms: Anemia, Sickle Cell
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to learn if it is possible and safe to treat persons with severe
      sickle cell disease (SCD) by bone marrow transplant (BMT) from human leukocyte antigen (HLA)
      half-matched related donors. Preparation before transplant includes the chemotherapy drugs
      hydroxyurea, fludarabine, thiotepa, anti-thymocyte globulin, and cyclophosphamide. It also
      includes radiation.
    

Detailed description: 
      The purpose of this study is to learn if it is possible and safe to treat persons with severe
      sickle cell disease (SCD) by bone marrow transplant (BMT) from human leukocyte antigen (HLA)
      half-matched related donors. Preparation before transplant includes the chemotherapy drugs
      hydroxyurea, fludarabine, thiotepa, anti-thymocyte globulin, and cyclophosphamide. It also
      includes radiation.

      Investigators also seek to understand the side effects of BMT in adolescents and young adults
      with SCD and measure how often serious side effects occur including those that are expected
      and unexpected. After transplant, investigators will measure the health of the body organs
      that ordinarily would have been damaged by having SCD in addition to testing the lungs,
      brain, and kidneys.
    

Intervention name(s): Bone Marrow Transplant (BMT); Hydroxyurea; Thiotepa; Fludarabine monophosphate; Cyclophosphamide; Rabbit Anti-thymocyte Globulin; Total Body Irradiation
Intervention type(s): Procedure; Drug; Drug; Drug; Drug; Other; Radiation
Intervention description(s): Participants will receive a bone marrow infusion from a human leukocyte antigen (HLA) mismatched donor through a central venous catheter.; Hydroxyurea is part of the bone marrow transplant preparative regimen. Hydroxyurea will be administered at a dose of 30 mg/kg orally as a single daily dose for 90 days (from day -100 to day-10). Hydroxyurea dosing will be based on adjusted body weight in participants weighing >125% ideal body weight.; Thiotepa is part of the bone marrow transplant preparative regimen. Thiotepa will be administered at a dose of 10mg/kg intravenously (IV) over 2 hours or per institutional guidelines on day -7. Thiotepa dosing will be based on adjusted body weight in patients weighing >125% ideal body weight.; Fludarabine is part of the bone marrow transplant preparative regimen. Fludarabine 30 mg/m2/day will be administered from day -7 to day -3 (for a total of 150 mg/m2 over 5 consecutive days) and administered intravenously (IV) over a minimum of 30 minutes. In participants weighing > 125% ideal body weight, fludarabine will be dose based upon adjusted body weight.; Cyclophosphamide is part of the bone marrow transplant preparative regimen. Cyclophosphamide will be administered on days -6 and -5 prior to bone marrow infusion at a dose of 14.5 mg/kg intravenously (IV) infused over 1-2 hours.
Post bone marrow infusion cyclophosphamide will be infused on days +3 (between 60 and 72 hours post marrow infusion) and +4 (approximately 24 hours after day +3 dose) at a dose of 50 mg/kg IV infused over 1-2 hours.
For participants weighing more than 125% of their ideal body weight, dosing will be based on adjusted ideal body weight.; Rabbit anti-thymocyte globulin (ATG) is part of the bone marrow transplant preparative regimen. It is an infusion of rabbit-derived antibodies against human T cells used for prevention of acute rejection in organ transplantation. Rabbit ATG will be administered on day -9 at 0.5 mg/kg and on days -8 and -7 at 2 mg/kg (for a total dose 4.5 mg/kg).; Participants will receive 200 cGy of TBI in a single fraction.
Intervention MeSH terms: Cyclophosphamide; Thiotepa; Fludarabine; Fludarabine phosphate; Hydroxyurea; Antilymphocyte Serum; Thymoglobulin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: bone marrow transplant