NCT05088356

Reduced Intensity Allogeneic HCT in Advanced Hematologic Malignancies w/T-Cell Depleted Graft

Phase 1 Trial for Patients With Advanced Hematologic Malignancies Undergoing Reduced Intensity Allogeneic HCT With a T-cell Depleted Graft With Infusion of Conventional T-cells and Regulatory T-cells

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 77 (estimated)
• Sponsor: Stanford University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Accepted

Summary

Reduced intensity conditioning (RIC) has emerged and been increasingly adopted as a modality to allow preparative conditioning pre transplant to be tolerated by older adults or those patients that are otherwise unfit for myeloablative conditioning. In this study, we aim to use RIC followed by matched related/unrelated donor, 7/8 matched related/unrelated donor, or haploidentical donor peripheral blood stem cell transplantation. Standard strategies to control the alloreactivity following HCT utilize immunosuppressive or cytotoxic medications. In this study, we explore donor graft engineering to enrich for immmunoregulatory populations to facilitate post transplantation immune reconstitution while minimizing graft versus host disease (GVHD) with post-transplant immunosuppressive agents.

Detailed description

The objectives for the study are listed below: Primary Objectives \*Determine the safety, and feasibility of administration of several dose combinations of conventional T-cells (Tcon) and regulatory T-cells (Treg) in subjects undergoing allogeneic hematopoietic cell transplantation (HCT) with related/unrelated HLA-matched or mismatched donors, or haploidentical donors with reduced intensity conditioning preparative regimen. Secondary Objectives * To determine the GVHD-free relapse-free survival (GRFS) post-HCT * To determine the overall survival (OS) post-HCT * To measure the incidence and severity of acute and chronic GVHD Exploratory Objectives * To measure the incidence of serious infections * To measure the incidence and timing of engraftment * To measure T cell immunity reconstitution parameters

Conditions

• Allogeneic Hematopoietic Cell Transplantation (HCT)
• Advanced Hematologic Malignancies
• Acute Leukemia
• Chronic Myelogenous Leukemia
• Myelodysplastic Syndromes
• Myeloproliferative Disorders

Interventions

Type	Name	Description
DRUG	Purified regulatory T-cells (Treg) plus CD34+ HSPC	Purified regulatory T-cells (Treg) plus CD34+ hematopoietic progenitor cells ("CD34+ HSPC"), followed by conventional T-cells (Tcon) Manufactured at SCTT Laboratory, dose 1x10\^6 cells/ kg to 3x10\^6 cells/kg
DRUG	Fludarabine	Fludarabine (160 mg/m2)
DRUG	Melphalan	Melphalan (50 mg/m2)
DEVICE	CliniMACS CD34 Reagent System	The CliniMACS® CD34 Reagent System is a medical device that is used in vitro to select and enrich specific cell populations is manufactured by Miltenyi Biotec
DRUG	Tacrolimus	4-6ng/mL
DRUG	Cyclophosphamide	40mg/kg
DRUG	Plerixafor	Dose 0.24 mg/kg, manufactured by Genzyme
DRUG	Filgrastim granulocyte colony-stimulating factor (G-CSF) or equivalent	Single-use vials contain either 300 mcg or 480 mcg filgrastim at a fill volume of 1.0 mL or 1.6 mL
DRUG	Thiotepa	Thiotepa 10 mg/kg
DRUG	Mycophenolate Mofetil (MMF)	MMF 1000 mg BID
DRUG	Ruxolitinib	Ruxolitinib 5 mg BID
DRUG	Sirolimus	5 - 8 ng/mL

Timeline

• Start date: 2021-09-07
• Primary completion: 2027-11-01
• Completion: 2027-11-01
• First posted: 2021-10-21
• Last updated: 2026-04-08

Locations

1 site across 1 country: United States

Regulatory

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