Overview

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

Status:
Recruiting

Trial end date:
2033-11-01

Target enrollment:

Participant gender:

Summary

Study Description: We propose to add JSP191, 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 JSP191 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 (JSP191) would increase proportion of patients with donor myeloid chimerism >=98% at 1 year post transplant Secondary Objectives: - To measure JSP191 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: - JSP 191 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

Phase:

Phase 1/Phase 2

Details

Lead Sponsor:

National Heart, Lung, and Blood Institute (NHLBI)

Treatments:

Alemtuzumab
Hydroxyurea
Plerixafor
Sirolimus