Non-myeloablative Haploidentical HCT Study for Patients With Sickle Cell Disease, Including Compromised Organ Function

Study Summary

Background: Sickle cell disease (SCD) is a genetic disorder where red blood cells, that carry oxygen, are stiff and become stuck in small blood vessels. As a result, affected patients can experience severe pain and serious organ damage. SCD can be cured with a hematopoietic cell transplant (HCT), that is, when they receive blood stem cells from a family donor. But HCT can also have serious side effects, especially in people with organ damage. Researchers want to find ways to make HCT safer for everyone. Objective: To test a new combination of drugs (briquilimab, abatacept, and alemtuzumab), used along with radiation, in people undergoing HCT for SCD. Eligibility: People aged 16 and older with SCD. They must be eligible for HCT and have a family member who is a good donor match. Donors must be aged 4 and older. Design: Participants with SCD will be screened. They will have blood tests and tests of organs including their heart and lung function. Donors will have blood drawn. Participants with SCD will have a tube inserted into a blood vessel in their chest (intravenously). This line will remain in place up to 2 months; it will be used to draw blood and administer the donor cells and other medications. Briquilimab will be administered intravenously 1 time, along with other drugs used to prepare for HCT. Participants will receive abatacept 6 times, from just before they receive their donor cells until 6 months after. Participants will undergo radiation therapy and take other drugs that are standard for HCT. Most HCT recipients remain in the hospital for about 30 days after HCT. Follow-up visits will continue for 5 years....

Primary Outcome

Number of participants at 1 year post stem cell transplant who have not experienced graft failure and who are without severe graft-versus-host disease (defined as grade 3 and higher acute GVHD). Graft failure is defined as the absence of or insufficient donor chimerism associated with the return of acute complications of sickle cell disease. As defined by CIMBTR criteria for Organ Stages of Acute GVHD: Grade III: Skin = Rash on \>50% of body surface; Liver = Total Bilirubin 6.1 - 15.0 mg/dL;

Conditions Studied

Interventions

• DRUG Non-myeloablative haploidentical peripheral blood stem cell transplantation with briquilimab and abatacept

Study Locations (1)