NCT05357482

Addition of JSP191 (C-kit Antibody) to Nonmyeloablative Hematopoietic Cell Transplantation for Sickle Cell Disease and Beta-Thalassemia

Addition of JSP191 (C-kit Antibody) to Non-myeloablative Hematopoietic Cell Transplantation For Sickle Cell Disease and Beta-Thalassemia

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 40 (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 an inherited disorder of the blood. It can damage a person s organs and cause serious illness and death. A blood stem cell transplant is the only potential cure for SCD. Treatments that improve survival rates are needed. Objective: To find out if a new antibody drug (briquilimab, JSP191) improves the success of a blood stem cell transplant Eligibility: People aged 13 or older who are eligible for a blood stem cell transplant to treat SCD. Healthy family members over age 13 who are matched to transplant recipients are also needed to donate blood. Design: Participants receiving transplants will undergo screening. They will have blood drawn. They will have tests of their breathing and heart function. They may have chest x-rays. A sample of marrow will be collected from a pelvic bone. Participants will remain in the hospital about 30 days for the transplant and recovery. They will have a large intravenous line inserted into the upper arm or chest. The line will remain in place for the entire transplant and recovery period. The line will be used to draw blood as needed. It will also be used to administer the transplant stem cells as well as various drugs and blood transfusions. Participants will also receive some drugs by mouth. Participants must remain within 1 hour of the NIH for 3 months after transplant. During that time, they will visit the clinic up to 2 times a week. Follow-up visits will include tests to evaluate participants mental functions. They will have MRI scans of their brain and heart.

Detailed description

Study Description: We propose to add briquilimab, an antibody targeting CD117 (c-Kit), to the 03-H-0170 regimen to improve myeloid chimerism, in patients considered at high risk for complications from or ineligible from standard myeloablative HSCT. Given the preclinical and clinical data, the addition of briquilimab has the potential to further deplete host lymphoid and myeloid cells to achieve a higher percentage of donor leukocyte engraftment without increased toxicity. Our prior non-myeloablative conditioning (NMA) regimen includes 1 mg/kg of alemtuzumab divided over 5 days, 300 cGy total body irradiation (TBI), and sirolimus for immune suppression. This regimen demonstrated a disease-free survival (DFS) and overall survival (OS) of 87% and 94% respectively, a 13% graft failure rate, no treatment related mortality (TRM), and no acute or chronic GVHD. A large proportion of patients achieves robust (\>=98%) donor myeloid chimerism early, but this proportion decreases to 57% at 1, 54% at 2, and 49% at 3, and 50% at 4 years post-transplant. Monoclonal antibodies (mAb) targeting human stem cells (HSCs) is one strategy to improve DFS and may have synergy when combined with TBI as part of transplant conditioning regimen. Objectives: Primary Objective: -To determine if addition of CD117 antibody (briquilimab) would increase proportion of patients with donor myeloid chimerism \>=98% at 1 year post transplant Secondary Objectives: * To measure briquilimab and alemtuzumab clearance at 1 and 2 years post transplant: * To compare CD14/15 and CD3 chimerism to protocol 03-H-0170 * Estimate the proportion of patients with donor myeloid chimerism at or above 75% * To assess the usual transplant related parameters, such as count recovery, transfusion support, rates of GVHD, viral/bacterial infections, and rates of transplant related and overall mortality, and compare to those results in 03-H-0170 Endpoints: Primary Endpoint: -percent myeloid (CD14/15) chimerism Secondary Endpoints: * Briquilimab antibody PK levels * Alemtuzumab levels * Percent T cell (CD3) chimerism * Day of neutrophil engraftment * Day of platelet engraftment * Rates of viral infection and/or reactivation * Rates of bacterial infection * Rates of acute and chronic GVHD * Transplant related mortality * Non-transplant related mortality * Rates of graft failure * Quality of life and neuropsychologic function

Conditions

• Sickle Cell Anemia
• Beta Thalassemia

Interventions

Type	Name	Description
RADIATION	TBI	300 cGy total body irradiation (TBI, day -2)
DRUG	Hydroxyurea	Optimized 4-12 weeks prior to planned transplant date
BIOLOGICAL	briquilimab	briquilimab, anti-CD117 monoclonal antibody at 0.6mg/kg at day -11 prior to infusion of allogeneic HSCs
DRUG	Filgrastim (G-CSF)	May be used to minimize the days of neutropenia, and may be administered beginning near day 10 post stem cell infusion at 5 mcg/kg (rounding to the nearest vial) at the discretion of investigator.
DRUG	Sirolimus	For immune suppression (day -1)
BIOLOGICAL	Alemtuzumab	Alemtuzumab 1 mg/kg of alemtuzumab divided over 5 days (-7 through -3),
DRUG	Plerixafor	For autologous HSC collection; dose of plerixafor at 240 mcg/kg (capped at 20mg)

Timeline

• Start date: 2022-05-12
• Primary completion: 2026-01-31
• Completion: 2027-01-31
• First posted: 2022-05-03
• Last updated: 2026-03-12

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study