Minimizing Toxicity in HLA-identical Sibling Donor Transplantation for Children With Sickle Cell Disease (SUN)

March 7, 2026 updated by: Robert Nickel
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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a prospective, multicenter phase II study of HLA-identical sibling donor HSCT in 30 pediatric patients with SCD using nonmyeloablative conditioning with alemtuzumab, total-body irradiation, and sirolimus. The primary Objective of this study is to determine if the SUN regimen can decrease the incidence of grade II-IV acute graft-versus host disease (GVHD) by day +100 while maintaining similar disease-free survival compared to establish HLA-identical donor hematopoietic stem cell transplant (HSCT) regimens in children with SCD. The secondary Objective is to determine if health-related quality of life (HRQoL) for children undergoing SUN HSCT is preserved during the early post-transplant time period. To determine if the SUN regimen can decrease the number of platelet transfusions compared to established HLA-identical HSCT regimens in children with SCD. The tertiary/Exploratory Objectives: To describe other markers of toxicity (duration of neutropenia, mucositis, length of hospitalization) and indicators of a successful HSCT (HRQoL at 1 year, proportion needing additional immunosuppression during the first year, proportion able to wean sirolimus at 1 year).

With protocol version 5.0, added new secondary objective to determine if the change from intravenous to subcutaneous alemtuzumab and the addition of post-HSCT G-CSF can decrease the incidence of poor donor engraftment.

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T3B 6A8
        • Recruiting
        • Alberta Children's Hospital
        • Contact:
          • Gregory Guilcher
        • Contact:
        • Principal Investigator:
          • Gregory Guilcher, MD
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • Recruiting
        • The Hospital for Sick Children
        • Contact:
        • Contact:
        • Principal Investigator:
          • Muhammad Ali, MD
  • United States
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20010
    • Illinois
      • Chicago, Illinois, United States, 60611
    • New York
      • New York, New York, United States, 10032
        • Recruiting
        • Columbia University
        • Contact:
        • Principal Investigator:
          • Monica Bhatia
    • North Carolina
      • Charlotte, North Carolina, United States, 28203
        • Recruiting
        • Levine Children's Hospital
        • Contact:
        • Principal Investigator:
          • Michael Kent, MD
    • Ohio
      • Columbus, Ohio, United States, 43205

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 25 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: SUN regimen

Alemtuzumab, 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).
Drug: Alemtuzumab, low dose total body irradiation, Sirolimus

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Acute GVHD
Time Frame: 100 days post transplant
Acute grade II-IV GVHD
100 days post transplant

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PedsQL 4.0 Measurement model for the Pediatric Quality of Life Inventory
Time Frame: Day +30, and day +100 post transplant
PedsQL 4.0 assessments of health related quality of life before/after transplant
Day +30, and day +100 post transplant
Poor donor engraftment
Time Frame: day +365
graft rejection, stem cell boost, or 1-year donor myeloid chimerism <50%
day +365

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Patient-Reported Outcomes Measurement Information System (PROMIS)
Time Frame: Day +30, and day +100 post transplant
PROMIS assessments of health related quality of life before/after transplant
Day +30, and day +100 post transplant
Platelet transfusion
Time Frame: 100 days post transplant
Number of platelet transfusions
100 days post transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Robert Nickel

Collaborators

The Hospital for Sick Children
Columbia University
Ann & Robert H Lurie Children's Hospital of Chicago
Nationwide Children's Hospital
Alberta Children's Hospital
Levine Children's Hospital
The Children's Hospital at Montefiore

Investigators

  • Principal Investigator: Robert Nickel, MD, Children's National Research Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 17, 2018

Primary Completion (Estimated)

November 1, 2030

Study Completion (Estimated)

November 1, 2030

Study Registration Dates

First Submitted

June 6, 2018

First Submitted That Met QC Criteria

July 13, 2018

First Posted (Actual)

July 16, 2018

Study Record Updates

Last Update Posted (Actual)

March 10, 2026

Last Update Submitted That Met QC Criteria

March 7, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB 10322

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Sickle Cell Disease

Clinical Trials on Alemtuzumab, low dose total body irradiation, Sirolimus

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Kenya

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe