Sickle Cell DiseasePhase 2SUNNCT03587272
Minimizing Toxicity in HLA-identical Sibling Donor Transplantation for Children With Sickle Cell Disease
A Phase 2 study testing Alemtuzumab, low dose total body irradiation, Sirolimus in people with Sickle Cell Disease, run by Robert Nickel at 7 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 2 to 25 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Alemtuzumab, low dose total body irradiation, Sirolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 7 sitesin 2 countries
- Study dates
- 17 Apr 2018to Nov 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Show all 17Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
7 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
7 sites in 2 countries
United States5 sites, 5 recruiting
- Recruiting
Levine Children's Hospital
Charlotte, North Carolina, 28203
Janice Hollifield, 980-442-2342, Janice.hollifield@atriumhealth.org
Michael Kent, MD
- Recruiting
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Olga Jonas, 312.227.4871, ojonas@luriechildrens.org
Ella Ramsey, dramsey@luriechildrens.org
- Recruiting
Nationwide Children's Hospital
Columbus, Ohio, 43205
Hemalatha Rangarajan, 614-355-1689, Hemalatha.Rangarajan@nationwidechildrens.org
Hemalatha Rangarajan, MD
- Recruiting
Columbia University
New York, New York, 10032
Jaclyn Dosik, 212-305-0866, jd3970@cumc.columbia.edu
Monica Bhatia
- Recruiting
Children's National Health System
Washington D.C., District of Columbia, 20010
Maryanne Odinakachukwu, 202-476-2957, modinakach@childrensnational.org
Fahmida Hoq, MBBS, MS, 202-476-3634, fhoq@childrensnational.org
Canada2 sites, 2 recruiting
- Recruiting
Alberta Children's Hospital
Calgary, Alberta, T3B 6A8
Gregory Guilcher
1-403-955-7272, Greg.Guilcher@AHS.ca
- Recruiting
The Hospital for Sick Children
Toronto, Ontario, M5G 1X8
Umer Muzzamil, 416-813-7654 ext. 414926, umer.muzzamil@sickkids.ca
Brandon Rothberg, 416-813-7654 ext. 202042, brandon.rothberg@sickkids.ca
About this 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).
Read the 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.
- Conditions
- Sickle Cell Disease
- Being tested
- Alemtuzumab, low dose total body irradiation, Sirolimus
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Alemtuzumab, low dose total body irradiation, SirolimusDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| SUN regimen | Experimental | 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). Receives: Drug: Alemtuzumab, low dose total body irradiation, Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Acute GVHD
Acute grade II-IV GVHD
Measured: 100 days post transplant
Secondary outcomes (2)
PedsQL 4.0 Measurement model for the Pediatric Quality of Life Inventory
PedsQL 4.0 assessments of health related quality of life before/after transplant
Measured: Day +30, and day +100 post transplant
Poor donor engraftment
graft rejection, stem cell boost, or 1-year donor myeloid chimerism <50%
Measured: day +365
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2018
- Study start17 Apr 2018
- Primary completionNov 2030 (estimated)
- Study completionNov 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Robert Nickel
- Sponsor type
- University, hospital or other
- Collaborators
- The Hospital for Sick Children, Levine Children's Hospital, Ann & Robert H Lurie Children's Hospital of Chicago, Nationwide Children's Hospital, Columbia University, Children's Hospital at Montefiore, Alberta Children's Hospital
- Responsible party
- Sponsor-investigator, Robert Nickel, Children's National Research Institute
- Investigators
- Robert Nickel, MD, Principal investigator, Children's National Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03587272
- Sponsor's protocol ID
- IRB 10322
- Acronym
- SUN
- Status last verified
- Mar 2026
- First submitted
- 6 Jun 2018
- Last updated
- 10 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Nickel RS, Abraham A, Chiang KY, Ali M, Rangarajan HG, Chaudhury S, Kent M, Odinakachukwu M, Kukadiya D, Malloy J, Zhang A, Hardy SJ, Guilcher GMT. Nonmyeloablative HLA-identical sibling transplant for sickle cell disease in children: a multicenter prospective study. Blood Adv. 2026 Jun 23;10(12):4160-4170. doi: 10.1182/bloodadvances.2025019567.
PubMed 41945757Leonard 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.
PubMed 36240296
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Minimizing Toxicity in HLA-identical Sibling Donor Transplantation for Children With Sickle Cell Disease
- ClinicalTrials.gov ID
- NCT03587272
- Acronym / sponsor ID
- SUN / IRB 10322
- Conditions
- Sickle Cell Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Robert NickelUniversity, hospital or other
- Collaborators
- The Hospital for Sick Children, Levine Children's Hospital, Ann & Robert H Lurie Children's Hospital of Chicago, Nationwide Children's Hospital, Columbia University, Children's Hospital at Montefiore, Alberta Children's Hospital
- Study start
- 17 Apr 2018 (actual)
- Primary completion
- Nov 2030 (estimated)
- Study completion
- Nov 2030 (estimated)
- First posted
- 16 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SUN regimen | Experimental | Drug: Alemtuzumab, low dose total body irradiation, SirolimusAlemtuzumab, 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). |
Who may qualify
- Ages
- 2 to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (17 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Alemtuzumab, low dose total body irradiation, SirolimusThe 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. | Drug | SUN regimen |
Primary outcome
Acute GVHD
Time frame: 100 days post transplant
Acute grade II-IV GVHD
2 secondary outcomes
PedsQL 4.0 Measurement model for the Pediatric Quality of Life Inventory
Time frame: Day +30, and day +100 post transplant
Poor donor engraftment
Time frame: day +365
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2026.
- Derived from this study: PubMed 41945757Nickel RS, Abraham A, Chiang KY, Ali M, Rangarajan HG, Chaudhury S, Kent M, Odinakachukwu M, Kukadiya D, Malloy J, Zhang A, Hardy SJ, Guilcher GMT. Nonmyeloablative HLA-identical sibling transplant for sickle cell disease in children: a multicenter prospective study. Blood Adv. 2026 Jun 23;10(12):4160-4170. doi: 10.1182/bloodadvances.2025019567.
- Derived from this study: PubMed 36240296Leonard 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Robert Nickel, MD principal investigator
Children's National Research Institute
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Alemtuzumab, low dose total body irradiation, Sirolimus in people with Sickle Cell Disease, run by Robert Nickel at 7 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Robert Nickel, MD (202-476-5000, RNickel@childrensnational.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Acute GVHD (time frame: 100 days post transplant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03587272, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2026.