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

Study point of contact

Robert Nickel, MD
202-476-5000
[email protected]
Allistair Abraham, MD
202-476-5000
[email protected]

Locations

4 United States sites

2 Canada sites

Age

2 to 25 Years

Genotypes

SS, SC

Phase

Phase 2

Study type

Interventional

Gender

All

Interventions

Drug

Compensation

Unknown

About the 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).

participation requirements

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.

– 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.

participation restrictions

– • 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.

Locations

  • Washington, District of Columbia, United States, Children's National Health System, 20010 [Recruiting]
  • Chicago, Illinois, United States, Ann & Robert H. Lurie Children's Hospital of Chicago, 60611 [Recruiting]
  • Charlotte, North Carolina, United States, Levine Children's Hospital, 28203 [Recruiting]
  • Columbus, Ohio, United States, Nationwide Children's Hospital, 43205 [Recruiting]
  • Calgary, Alberta, Canada, Alberta Children's Hospital, T3B 6A8 [Recruiting]
  • Toronto, Ontario, Canada, The Hospital for Sick Children, M5G 1X8 [Recruiting]