Minimizing Toxicity in HLA-identical Related Donor Transplantation for Children With Sickle Cell Disease

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). To evaluate event-free survival (EFS), toxicity, health-related quality of life (HRQL), and transfusion burden among pediatric patients with SCD using a chemotherapy-free nonmyeloablative regimen. Baseline HRQL was compared with scores at day +30 and day +100 post-HSCT using the PedsQL and PROMIS measures. EFS was defined by any of the following events: death, graft failure (myeloid donor chimerism <10%), or GVHD.

CT.gov Identifier

NCT03587272

EudraCT Identifier

N/A

CTIS:

N/A

Collaborator

Columbia University, Nationwide Children's Hospital, Ann & Robert H. Lurie Children's Hospital of Chicago, Montefiore Medical Center (MMC), Levine Children's Hospital (LCH), Children's National Hospital-Main Hospital, Alberta Children's Hospital (ACH)

Study Contact Information

N/A

Recruiting

Study Details

Diseases

Beta-Hemoglobinopathies

Study Drug

Alemtuzumab, Harvest Moon Pharmaceuticals

Radiation therapy

Sirolimus, J&J

Haploidentical hematopoietic stem cell transplantation

Genes

HBB

Study Dates

Apr 2018 - Nov 2030

Sex

Female & Male

Age

2 - 25 Years

Inclusion and Exclusion Criteria

Inclusion Criteria:

Patients with genotypes hemoglobin SS and Sß0 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, Sß+ 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. 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.

Exclusion Criteria:

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 nucleic acid amplification test (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 Echocardiogram.
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.

Protocol Summary

Study Locations

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