Minimizing Toxicity in HLA-identical Sibling Donor Transplantation for Children With Sickle Cell Disease
SUN
1 other identifier
interventional
100
2 countries
7
Brief Summary
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Apr 2018
Longer than P75 for phase_2
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 17, 2018
CompletedFirst Submitted
Initial submission to the registry
June 6, 2018
CompletedFirst Posted
Study publicly available on registry
July 16, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
November 1, 2030
March 10, 2026
March 1, 2026
12.6 years
June 6, 2018
March 7, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Acute GVHD
Acute grade II-IV GVHD
100 days post transplant
Secondary Outcomes (2)
PedsQL 4.0 Measurement model for the Pediatric Quality of Life Inventory
Day +30, and day +100 post transplant
Poor donor engraftment
day +365
Other Outcomes (2)
Patient-Reported Outcomes Measurement Information System (PROMIS)
Day +30, and day +100 post transplant
Platelet transfusion
100 days post transplant
Study Arms (1)
SUN regimen
EXPERIMENTALAlemtuzumab, low dose total body irradiation, Sirolimus 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).
Interventions
The conditioning regimen (SUN regimen) will consist of alemtuzumab daily for 5 days (total dose 1 mg/kg) and low dose total body irradiation (TBI) 300 cGY on Day -2 with gonadal shielding if possible. The HSCT graft will be G-CSF mobilized PBSCs with minimum CD34+ of 5 x106/kg recipient weight, goal of 10 x 106/kg (no upper limit). A peripheral blood stem cell (PBSC) graft was selected as it engrafts faster than bone marrow and would lead to shorter period of neutropenia and infection and less thrombocytopenia and need for platelet transfusion. GVHD prophylaxis will be sirolimus with a loading dose 3 mg/m2 on day -1. Sirolimus will be continued at 1 mg/m2/day starting on day 0 and dose adjusted to maintain a target trough level 5-15 ng/mL for the first 3 months and 5-10 ng/mL for the remainder of the first year.
Eligibility Criteria
You may qualify if:
- 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).
- +2 more criteria
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Robert Nickellead
- The Hospital for Sick Childrencollaborator
- Levine Children's Hospitalcollaborator
- Ann & Robert H Lurie Children's Hospital of Chicagocollaborator
- Nationwide Children's Hospitalcollaborator
- Columbia Universitycollaborator
- The Children's Hospital at Montefiorecollaborator
- Alberta Children's Hospitalcollaborator
Study Sites (7)
Children's National Health System
Washington D.C., District of Columbia, 20010, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611, United States
Columbia University
New York, New York, 10032, United States
Levine Children's Hospital
Charlotte, North Carolina, 28203, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
Alberta Children's Hospital
Calgary, Alberta, T3B 6A8, Canada
The Hospital for Sick Children
Toronto, Ontario, M5G 1X8, Canada
Related Publications (1)
Leonard A, Furstenau D, Abraham A, Darbari DS, Nickel RS, Limerick E, Fitzhugh C, Hsieh M, Tisdale JF. Reduction in vaso-occlusive events following stem cell transplantation in patients with sickle cell disease. Blood Adv. 2023 Jan 24;7(2):227-234. doi: 10.1182/bloodadvances.2022008137.
PMID: 36240296DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Robert Nickel, MD
Children's National Research Institute
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
June 6, 2018
First Posted
July 16, 2018
Study Start
April 17, 2018
Primary Completion (Estimated)
November 1, 2030
Study Completion (Estimated)
November 1, 2030
Last Updated
March 10, 2026
Record last verified: 2026-03