Reducing toxicity in sibling donor transplants for children with sickle cell disease

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This multicenter phase II study aims to evaluate the effectiveness of HLA-identical sibling donor transplantation using a nonmyeloablative approach with alemtuzumab, low dose total-body irradiation, and sirolimus in children with sickle cell disease. The primary goal is to reduce the incidence of acute graft-versus-host disease while maintaining disease-free survival rates. Secondary objectives include assessing health-related quality of life and the need for platelet transfusions post-transplant. The study will also explore additional markers of toxicity and indicators of successful transplantation.

Why it matters

Who can join: the full rules

Inclusion criteria:

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.

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 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 it's running

• Children's National Health System
  Washington D.C., District of Columbia, United States Recruiting
• Ann & Robert H. Lurie Children's Hospital of Chicago
  Chicago, Illinois, United States Recruiting
• Columbia University
  New York, New York, United States Recruiting
• Levine Children's Hospital
  Charlotte, North Carolina, United States Recruiting
• Nationwide Children's Hospital
  Columbus, Ohio, United States Recruiting
• Alberta Children's Hospital
  Calgary, Alberta, Canada Recruiting

Study contacts

• Principal investigator: Robert Nickel, MD — Children's National Research Institute
• Study coordinator: Robert Nickel, MD
• Email: RNickel@childrensnational.org
• Phone: 202-476-5000

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Other studies for the same condition or treatment. Recruiting studies are listed first.

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.