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

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.

Conditions

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

Interventions

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

Sponsors & Collaborators

• Orca Biosystems, Inc.

  collaborator INDUSTRY

• Stanford University

  lead OTHER

Principal Investigators

• Everett Meyer, MD,PhD · Stanford Universiy

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2021-09-07

Primary Completion

2028-05-31

Completion

2028-05-31

FDA Drug

Yes

FDA Device

Yes

Countries

• United States

Study Locations