NCT06145282

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

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

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 6 (actual)
• Sponsor: National Heart, Lung, and Blood Institute (NHLBI) · NIH
• Sex: All
• Age: 4 Years – 100 Years
• Healthy volunteers: Not accepted

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....

Detailed description

Study Description: Haploidentical hematopoietic cell transplantation offers a widely available curative option for individuals with sickle cell disease. The goal is to reverse SCD while avoiding unacceptable graft rejection, graft-versus-host disease, infectious complications, and hyperinflammatory responses. We hypothesize that a moderate amount of immunosuppression will maximize efficacy while avoiding unacceptable toxicity. Objectives: Primary Objective: -Evaluate the regimen success rate where success is defined as successful engraftment (persistent donor chimerism and free of acute SCD complications) and absence of acute grade 3 or higher GVHD or moderate to severe chronic GVHD evaluated at 1 year posttransplant. Secondary Objectives: * Event-free survival and overall survival. * Incidence of recipient-type hemoglobin defined as HbS \>10% when donors have HbAA and HbS \>50% when donors have sickle cell trait (HbAS). * The proportion of patients with myeloid chimerism \>= 95% at 1 and 2 years post-HCT. * Incidence of acute and chronic GVHD. * Prevalence of donor type hemoglobin at 1-year post-transplant in SCD patients who have not been transfused in the previous 3 months. * Incidence of viral reactivation and disease. * Incidence of autoimmune and hyperinflammatory complications. * Incidence of hematologic malignancies. * Transplant-related mortality. Exploratory Objective: * Perform gene therapy research involving cell culture or genetic manipulation to produce normal or therapeutic hemoglobin on excess autologous CD34+ cells collected from recipients. * Evaluate the impact of this non-myeloablative conditioning regimen on organs including the heart, lung, kidneys, liver, brain, neurocognitive function, and endocrine organs * Evaluate the impact of this non-myeloablative conditioning regimen on quality of life. Endpoints: Primary Endpoint: -The percentage of SCD patients at 1 year (+/- 3 months) posttransplant who have not experienced graft failure and who are without severe graft-versus-host disease (defined as grade 3 and higher acute GVHD and moderate to severe chronic GVHD). Secondary Endpoints: * Total hemoglobin and percent HbS levels * Percent donor myeloid chimerism and donor CD3 chimerism * Day of neutrophil engraftment * Day of platelet engraftment * RBC transfusion requirement * Rates of acute and chronic GVHD * Rates of viral reactivation and disease * Rates of autoimmune and hyperinflammatory complications * Transplant-related mortality * Non-transplant-related mortality * Rates of graft failure * Rates of leukemia and related disorders Exploratory Endpoint: Completion of gene therapy research involving cell culture or genetic manipulation to produce normal or therapeutic hemoglobin on excess autologous CD34+ cells collected from recipients. Organ function and quality of life

Conditions

• Sickle Cell Disease

Interventions

Type	Name	Description
DRUG	Non-myeloablative haploidentical peripheral blood stem cell transplantation with briquilimab and abatacept	All participants will receive the same dose of the investigational briquilimab antibody and abatacept added to the NIH-established regimen of alemtuzumab-TBI-sirolimus and infusion of filgrastim-mobilized peripheral blood hematopoietic cells from haploidentical related donors.

Timeline

• Start date: 2023-12-28
• Primary completion: 2025-10-27
• Completion: 2027-11-26
• First posted: 2023-11-24
• Last updated: 2025-12-19

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study