RightFit
RecruitingPhase 2

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

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
2 Years to 25 Years
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

Not stated in the study description — ask the study team about visits and procedures.

Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests whether a sibling donor transplant can cause less harm while still curing sickle cell disease in children. The donor must be a brother or sister with matching tissue markers, called HLA. The treatment uses alemtuzumab, low-dose radiation to the whole body, and sirolimus.

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).

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Children must have at least one of the health problems below. Some rules differ by their type of sickle cell disease.
  • For hemoglobin SS or Sβ0: a past stroke seen on a brain MRI, including a silent stroke that meets the study's scan rules; or high blood flow on two brain ultrasound tests (at least 200 cm/sec without imaging or 185 cm/sec with imaging). For other types, such as SC or Sβ+: a stroke that caused symptoms.
  • At least two episodes of acute chest syndrome, a serious lung problem. For SS or Sβ0, these can be at any time. For other types, they must be in the past two years.
  • At least three sickle cell pain events treated with opioid pain drugs or pain drugs given through a vein. For SS or Sβ0, these can be at any time. For other types, they must be in the past year.
  • Any hospital stay for sickle cell pain or acute chest syndrome while taking hydroxyurea.
  • At least two erections lasting four hours or longer, or needing emergency care.
  • Regular red blood cell transfusions: at least eight in the past 12 months.
  • At least two times when blood trapped in the spleen required a red blood cell transfusion, or spleen removal after at least one such event.

Who can't join

  • Expected to live less than six months, pregnant, or breastfeeding.
  • An infection that keeps getting worse despite treatment within one month before transplant preparation. Fever or a possible minor infection must clear before preparation starts. HIV or active hepatitis B or C also rules out joining.
  • Liver blood tests showing direct bilirubin above 1.5 mg/dL or liver enzymes above five times the normal upper limit for age.
  • Low heart pumping strength on a heart ultrasound: shortening fraction below 25% or ejection fraction below 50%.
  • Low kidney filtering ability: estimated creatinine clearance below 60 mL/min/1.73 m².
  • Poor lung function: a gas-transfer test (DLCO), adjusted for hemoglobin, below 35%; oxygen saturation below 85%; or blood oxygen pressure below 70.
  • Past antibodies that attack the donor's red blood cells, even if a current test is negative, or a major ABO blood-type mismatch with the donor.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

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 sites (5)

DC

IL

NC

NY

OH