NCT04018937

Early Human Leukocyte Antigen (HLA) Matched Sibling Hematopoietic Stem Cell Transplantation

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

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 43 (actual)
• Sponsor: Emory University · Academic / Other
• Sex: All
• Age: 2 Years – 13 Years
• Healthy volunteers: Not accepted

Summary

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 2 years after transplant.

Detailed description

The use of HLA matched sibling donor (MSD) hematopoietic stem cell transplantation (HSCT) for sickle cell disease (SCD) is evolving. Because of the low risk for graft versus host disease (GVHD) associated with younger age, HSCT is increasingly being performed prior to adolescence. The use of less gonadotoxic reduced intensity regimens (RIC) are more commonly be utilized to lessen the risk for infertility. Finally, with the recognition that most children, even those who have asymptomatic to relatively mild courses, will develop debilitating morbidities as adults and ultimately suffer an early death, HSCT is being offered to children across a wider spectrum of SCD severity. Long reserved for severely affected children, HSCT is being performed for a growing number of less severely affected children, as well as children without disease manifestation. This trial is designed to prospectively assess HSCT under these conditions. Eligibility will be limited to children less than 13 years of age who have an HLA MSD. A RIC regimen - fludarabine, alemtuzumab and melphalan (FAM) - will be employed. Finally, SCD severity criteria will be broadened to include less severely affected children as well as those who are severely affected. This study has the following two specific aims: Specific Aim #1: To prospectively assess the safety and efficacy of HSCT using FAM conditioning in children with SCD of varying severity who are under 13 years of age. Specific Aim #2: To address current gaps in our understanding of the long-term effects of HSCT in children with SCD, by longitudinally assessing sickle cell related cerebrovascular disease, sickle cell related nephropathy and health related quality of life.

Conditions

• Sickle Cell Disease

Interventions

Type	Name	Description
DRUG	Alemtuzumab	Alemtuzumab will be administered by either subcutaneous (SQ) injection or IV. A test dose of alemtuzumab, 3 mg, is administered on the first day. If the test dose is tolerated, administration of three treatment doses will begin within 24 hours. The three treatment doses will be administered on consecutive days. On the first day, 10 mg/m2 will be given, 15 mg/m\^2 the second and 20 mg/m\^2 the third. Alemtuzumab will be started between Days -22 and -20, but all doses (test dose and three treatment doses) should be completed by Day -18.
DRUG	Fludarabine	Fludarabine will be administered at 30 mg/m\^2 IV daily for five days (Days -7 to -3).
DRUG	Melphalan	Melphalan will be administered at 140 mg/m\^2 IV on Day -3 following fludarabine administration.

Timeline

• Start date: 2019-03-22
• Primary completion: 2026-11-01
• Completion: 2026-11-01
• First posted: 2019-07-15
• Last updated: 2024-11-25

Locations

15 sites across 2 countries: United States, Canada

Regulatory

• FDA-regulated drug study