Early HLA Matched Sibling Hematopoietic Stem Cell Transplantation for Children With Sickle Cell Disease: A Sickle Transplant Advocacy and Research Alliance (STAR) Trial

About the study

This study aims to enroll 58 pre-adolescent (<13 years) pediatric participants with sickle
cell disease (SCD) who have a pre-adolescent sibling bone marrow donor. All participants will
go through a pre-transplant evaluation to find out if there are health problems that will
keep them from being able to receive the transplant. It usually takes 2 to 3 months to
complete the pre-transplant evaluation and make the arrangements for the transplant. Once
they are found to be eligible for transplant, participants will be admitted to the hospital
and will start transplant conditioning. Conditioning is the chemotherapy and other medicines
given to prepare them to receive donor cells. It prevents the immune system from rejecting
donor cells. Conditioning will start 21 days before transplant. Once they complete
conditioning, participants will receive the bone marrow transplant. After the transplant,
participants will stay in the hospital for 4-6 weeks. After they leave the hospital,
participants will be followed closely in the clinic. Outpatient treatment and frequent clinic
visits usually last 6 to 12 months. Routine medical care includes at least a yearly
examination for many years after transplant by doctors and nurses familiar with sickle cell
disease and transplant. The researchers will collect and study information about participants
for 5 years after transplant.

Study point of contact

Ann Haight, MD
Shelley Mays


11 United States sites


2 to 13 Years




Phase 2

Study type








participation requirements

– Patients must be at least 2 years and less than 13 years old and have a sickle

– Patient must have an HLA identical sibling donor who is less than 13 years old.
Sibling donors must not have any form of SCD. It is acceptable for the donor to carry
a hemoglobinopathy trait.

– Patients must meet criteria for symptomatic SCD as defined below.

– Severe disease:

– Previous clinical stroke, defined as a neurological deficit lasting longer
than 24 hours plus new finding on head CT or brain MRI/MRA.

– Progressive silent cerebral infarction, as evidenced by serial MRI scans
that demonstrate the development of a succession of lesions (at least two
temporally discreet lesions, each measuring at least 3 mm in greatest
dimension on the most recent brain MRI/MRA) or the enlargement of a single
lesion, initially measuring at least 3 mm). Lesions must be visible on
T2-weighted MRI sequences.

– Abnormal TCD testing (confirmed elevated velocities in any single vessel of
TAMMV > 200 cm/sec for non-imaging TCD)

– Significant vasculopathy on MRA (greater than 50% stenosis of > 2 arterial
segments or complete occlusion of any single arterial segment).

– Frequent (at least 3 per year for preceding 2 years) painful vaso-occlusive
episodes (defined as episode lasting at least 4 hours and requiring
hospitalization or outpatient treatment with parenteral opioids). If patient
is on hydroxyurea and its use has been associated with a decrease in the
frequency of episodes, the frequency should be gauged from the 2 years prior
to the start of hydroxyurea.

– Recurrent (at least 3 in lifetime) acute chest syndrome events which have
necessitated erythrocyte transfusion therapy.

– Any combination of at least 3 acute chest syndrome episodes and
vaso-occlusive pain episodes (defined as above) yearly for 3 years. If
patient is on hydroxyurea and its use has been associated with a decrease in
the frequency of episodes, the frequency should be gauged from the 3 years
prior to the start of hydroxyurea.

– Less severe disease: to qualify as having less severe disease, patients must not
meet criteria for severe disease and must have one of the following:

– Asymptomatic cerebrovascular disease, as evidenced by one the following:
Silent cerebral infarction with at least one lesion measuring at least 3 mm
in one dimension that is visible on two planes on the most recent brain MRI,
or, cerebral arteriopathy, as evidenced by conditional TCD (TAMMV>170cm/sec
but <200cm/sec) on two separate scans >2 weeks apart). If patient has a
conditional TCD, then a brain MRI/MRA to evaluate for vasculopathy is

– 2 or more painful vaso-occlusive episodes (in lifetime) requiring
hospitalization or outpatient treatment with parenteral opioids.

– 2 or more episodes of acute chest syndrome (in lifetime) irrespective of SCD
modifying therapy administered.

– Any combination of at least 3 acute chest syndrome episodes and
vaso-occlusive pain episodes (defined as above, lifetime).

– No clinical manifestations of HbSS and HbSβ°thalassemia

– Participant’s parent or legal guardian must sign a written informed consent. Assent,
when appropriate, will be obtained according to institutional guidelines.

– Patient must have been evaluated and parent(s)/legal guardian, and the patient as age
appropriate as determined by the treating center, adequately counseled regarding
treatment options for SCD by a pediatric hematologist.

– Co-enrollment on STAR Project Sickle Cure (PSC) study is required for sites that are
activated and participating in the study.

participation restrictions

– Bridging (portal to portal) fibrosis or cirrhosis of the liver.

– Parenchymal lung disease stemming from SCD or other process defined as a diffusing
capacity of the lungs for carbon monoxide (DLCO; corrected for hemoglobin) or forced
vital capacity of less than 45% of predicted. Children unable to perform pulmonary
function testing will be excluded if they require daytime oxygen supplementation.

– Renal dysfunction with an estimated glomerular filtration rate (GFR) < 50% of predicted normal for age. - Cardiac dysfunction with shortening fraction < 25%. - Neurologic impairment other than hemiplegia, defined as full-scale intelligence quotient (IQ) of less than or equal to 70, quadriplegia or paraplegia, or inability to ambulate. - Lansky functional performance score < 70%. - Patient is HIV infected. - Donor is HIV infected. - Patient with unspecified chronic toxicity serious enough to detrimentally affect the patient's capacity to tolerate HSCT. - Patient's parent(s) or legal guardian is unable to understand the nature and the risks inherent in the HSCT process. - History of lack of adherence with medical care that would jeopardize transplant course. - Donor who for psychological, physiologic, or medical reasons is unable to tolerate a bone marrow harvest or receive general anesthesia. - Active viral, bacterial, fungal or protozoal infection. - Patients with viral upper respiratory tract infections should be asymptomatic for at least 7 days prior to enrollment. PCR testing for respiratory viruses (nasopharyngeal sample) should be negative at the start of the conditioning regimen. Exceptions may be made in patients with prolonged carriage (repeatedly positive over many weeks) of rhinovirus. These exceptions should be discussed with and approved by both study co-chairs and STAR Medical Director.


  • New Haven, Connecticut, United States, Yale University, 06520 [Recruiting]
  • Washington, District of Columbia, United States, Children's National Health System, 20010 [Recruiting]
  • Atlanta, Georgia, United States, Children's Healthcare of Altanta, 30322 [Recruiting]
  • Jackson, Mississippi, United States, University of Mississippi Medical Center, 39216 [Recruiting]
  • Hackensack, New Jersey, United States, Columbia University Medical Center, 07601 [Recruiting]
  • New York, New York, United States, Columbia University Medical Center, 10032 [Recruiting]
  • Chapel Hill, North Carolina, United States, University of North Carolina Medical Center, 27514 [Recruiting]
  • Kent, Ohio, United States, University Hospitals Kent Health Center, 44240 [Recruiting]
  • Philadelphia, Pennsylvania, United States, Children's Hospital of Philadelphia, 19104 [Recruiting]
  • Charleston, South Carolina, United States, Medical University of South Carolina, 29425 [Recruiting]
  • San Antonio, Texas, United States, Methodist Healthcare Systems, 78229 [Recruiting]
Last updated 2021-07-13