NCT07257419

CD45RA-depleted CD19-CAR T Cell Consolidation After TCRαβ+/CD19 B Cell-depleted Haploidentical Hematopoietic Cell Transplantation for Relapsed/Refractory CD19+ ALL and Lymphoma

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: St. Jude Children's Research Hospital · Academic / Other
• Sex: All
• Age: 21 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to learn more about newer methods of transplanting blood cells donated by a partially matched family member to children with high-risk CD19 positive leukemia ALL. Primary Objective: \- To assess the safety and feasibility of combining CD19-CAR(Mem) T cells after TCRαβ+/CD19 depleted haploidentical donor transplantation for pediatric patients with relapsed/refractory CD19+ B-cell malignancies. Secondary Objectives: * To estimate 1-year post-transplant overall survival, event-free survival, and GVHD-free relapse-free survival (GRFS). * To estimate cumulative incidence of engraftment, acute and chronic GVHD, and immune-related adverse events, including CRS and ICANS.

Detailed description

This is a Phase I study evaluating the addback of CD19-CAR(Mem) T cells after TCRαβ+/CD19 B cell depleted haploidentical donor transplantation for pediatric patients with relapsed/refractory CD19+ B-cell malignancies. Donors that meet eligibility criteria will be consented to undergo two separate collections: 1) G-CSF mobilized stem cell graft via apheresis for progenitor cell infusion and 2) Non-mobilized peripheral blood mononuclear cells (PBMC) via apheresis for subsequent CAR T-cell manufacturing and DLI if needed. Patients that meet eligibility criteria to receive therapy will be consented to proceed on study. Treatment will include a conditioning chemotherapy preparative regimen followed by infusion of TCRαβ/CD19 B cell depleted progenitor cell infusion on day 0. Then as early as day + 14 patients will receive the previously manufactured CD19-CAR(Mem) T cell product. Patients will then be monitored for safety and efficacy of the infused CAR T-cell product, as well as collection of correlative samples.

Conditions

• Relapsed Pediatric ALL
• Hematopoietic Cell Transplantation
• Hematologic Malignancy

Interventions

Type	Name	Description
DRUG	Anti-Thymocyte Globulin (Rabbit)	Days -10, -11, -12.
DRUG	Cyclophosphamide	60 mg/kg intravenous once daily on day -9.
DRUG	Fludarabine	30 mg/m2 intravenous once daily for \>10 kg, 1 mg/kg intravenous once daily for ≤10 kg on days -4, -5, -6, -7, -8.
DRUG	Thiotepa	5 mg/kg intravenous twice daily on day -3.
DRUG	Mesna	Mesna is planned to be administered at 15 mg/kg/dose prior to cyclophosphamide and at approximately 3, 6, and 9 hours after the cyclophosphamide infusion, to give a 1:1 ratio of mesna:cyclophosphamide.
DRUG	Melphalan	70 mg/m2 intravenous once daily for \>10 kg, 2.3 mg/kg intravenous once daily for ≤10 kg on days -1, and -2.
DRUG	Filgrastim	G-CSF\* 10 mcg/kg/day SC days 0, -1, -2, -3, -4, -5.
DEVICE	CliniMACS System	The mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest.

Timeline

• Start date: 2026-06-03
• Primary completion: 2031-12-01
• Completion: 2035-12-01
• First posted: 2025-12-02
• Last updated: 2026-04-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study
• FDA-regulated device study