Title (BMT CTN 0601) Unrelated Donor Reduced Intensity Bone Marrow Transplant for Children with Severe Sickle Cell Disease
Principal Investigator Barbara Bambach, MD
Study Number 147308
The study is a Phase II, single arm, multi-center trial. It is designed to estimate the efficacy and toxicity of unrelated donor HCT in patients with SCD and high risk features who are between 3 and 16 years of age. The primary objective is to determine event-free survival (EFS) at 1 year after unrelated donor (URD) hematopoietic stem cell transplantation (HCT) using bone marrow (BM) in patients with sickle cell disease (SCD). Death, disease recurrence or graft rejection by 1 year will be considered events for this endpoint. Secondary objectives include determining the effect of HCT on clinical and laboratory manifestations or severe sickle cell disease including stroke and determining the incidence of other transplant related outcomes.
- Patients 3-19.75 years at age of enrollment. Patients must have symptomatic SCD and have ONE OR More of the following clinical complications:
- A. i) a clinically significant neurologic event (stroke) or any neurologic defect lasting > 24 hours that is accompanied by an infarct on cerebral magnetic resonance imaging (MRI); OR (ii) patients who have a TCG velocity that exceeds 200 cm/sec by the non-imaging technique (or TCD measurement of > 185 cm/sec by the imaging technique) measured at a minimum of 2 separate occasions one month or more apart; OR
- B.) Minimum of two episodes of acute episodes of acute chest syndrome within the preceding 2-year period defined as new pulmonary alveolar consolidation involving at least one complete lung segment (associated with acute symptoms including fever, chest pain, tachypnea per age adjusted normal, intercostal retractions/nasal flaring/use of accessory muscles of respiration, wheezing, rales or cough that is not attributed to asthma or bronchiolitis) despite adequate supportive care measures;
- iii) History of 3 or more severe pain events per year in the 2 years prior to enrollment despite adequate supportive care measures.
- Lansky performance score must be >= 40.
- Patients must have an unrelated adult BM donor who is HLA-matched at 8 of 8 HLA-A, -B, -C and -DRBI at high resolution using DNA based typing). The UCB unit must contain a precryopreserved total nucleated cell dose (TNC) of at least 3.0 x 10^7 per kilogram.
- Patients must have adequate physical functions as measured by cardiac, pulmonary, renal and hepatic (see page 2-3).
- If the patient has been receiving chronic transfusion therapy for >= 1 year AND has clinical evidence of iron overload, a liver biopsy shall be obtained. Histologic exam of the liver must document absence of bridging fibrosis or cirrhosis of the liver. In other cases, a liver biopsy is optional.
- Hb S must be <= 45% 7 days prior to initiation of alemtuzumab.
- Patients with cirrhosis of the liver, with uncontrolled bacterial, viral or fungal infection on the past month, or seropositivity for HIV are excluded
- Patients with HLA-matched family donors, or who have received prior HCT and females who are pregnant or breast feeding are excluded