Minimizing Toxicity in HLA-identical Sibling Donor Transplantation for Children With Sickle Cell Disease
About this study
This multisite prospective study seeks to determine if HLA-identical sibling donor transplantation using alemtuzumab, low dose total-body irradiation, and sirolimus (Sickle transplant Using a Nonmyeloablative approach, "SUN") can decrease the toxicity of transplant while achieving a high cure rate for children with sickle cell disease (SCD).
- Condition
- Sickle Cell Disease
- Tested
- Alemtuzumab, low dose total body irradiation, Sirolimus
- Sponsor
- Robert Nickel
Who can join
- Age
- 2 to 25 years
- Sex
- All sexes
- Healthy volunteers
- Not accepted
Inclusion 16
- Minimum age: 2 years
- Maximum age: 25 years
- Study condition: Sickle Cell Disease
- Patients with genotypes hemoglobin SS and Sβ0 thalassemia must have at least one of the following:
- History of an abnormal transcranial Doppler measurement defined as TCD velocity ≥200 cm/sec by the non-imaging technique (or ≥185 cm/sec by the imaging technique) measured at a minimum of two separate occasions.
- History of cerebral infarction on brain MRI (overt stroke, or silent stroke if ≥3 mm in one dimension, visible in two planes on fluid-attenuated inversion recovery T2-weighted images).
- History of two or more episodes of acute chest syndrome (ACS) in lifetime.
- History of three or more SCD pain events requiring treatment with an opiate or IV pain medication (inpatient or outpatient) in lifetime.
- History of any hospitalization for SCD pain or ACS while receiving hydroxyurea treatment.
- History of two or more episodes of priapism (erection lasting ≥4 hours or requiring emergent medical care).
- Administration of regular RBC transfusions (≥8 transfusions in the previous 12 months).
- At least two episodes of splenic sequestration requiring red blood cell transfusion or splenectomy after at least one episode of splenic sequestration.
- Patients with all other sickle genotypes (hemoglobin SC, Sβ+ thalassemia) must have at least one of the following:
- Clinically significant neurologic event (overt stroke).
- History of two or more episodes of ACS in the 2-years period preceding enrollment.
- History of three or more SCD pain events requiring treatment with an opiate or IV pain medication (inpatient or outpatient) in the 1-year period preceding enrollment.
Exclusion 9
- General: Life expectancy less than 6 months. Pregnant or breastfeeding patients.
- Infection Disease: Uncontrolled bacterial, viral or fungal infections (undergoing appropriate treatment and with progression of clinical symptoms) within 1 month prior to conditioning.
- Patients with febrile illness or suspected minor infection should await clinical resolution prior to starting conditioning.
- Patients with confirmed seropositivity for HIV and patients with active Hepatitis B or C determined by serology and/or NAAT are excluded.
- Liver: Direct (conjugated) bilirubin \> 1.5 mg/dL, transaminases \>5x upper limit of normal for age.
- Cardiac: Left ventricular shortening fraction \<25% or ejection fraction \<50% by ECHO.
- Kidney: Estimated creatinine clearance less than 60 mL/min/1.73m2.
- Pulmonary function: Diffusion capacity of carbon monoxide (DLCO) \<35% (adjusted for hemoglobin). Baseline oxygen saturation \<85% or PaO2 \<70.
- Heme: History of RBC alloantibodies against donor RBC antigens (even if current antibody screen is negative). Major ABO incompatibility with donor.
Where
7 sites, 7 recruiting
Alberta Children's Hospital
Calgary, Alberta, Canada
The Hospital for Sick Children
Toronto, Ontario, Canada
Levine Children's Hospital
Charlotte, North Carolina, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
Columbia University
New York, New York, United States
and 1 more site on ClinicalTrials.gov
Contact
-
Robert Nickel, MD
202-476-5000 RNickel@childrensnational.org
-
Maryanne Odinakachukwu
202-476-2957 modinakach@childrensnational.org
Potential match only. Final eligibility is determined by the study team.