Provision of TCRγδ T Cells and Memory T Cells Plus Selected Use of Blinatumomab in Naïve T-cell Depleted Haploidentical Donor Hematopoietic Cell Transplantation for Hematologic Malignancies Relapsed or Refractory Despite Prior Transplantation

Summary

This study seeks to examine treatment therapy that will reduced regimen-related toxicity and relapse while promoting rapid immune reconstitution with limited serious graft-versus-host-disease (GVHD) and also improve disease-free survival and quality of life. The investigators propose to evaluate the safety and efficacy of selective naive T-cell depleted (by TCRɑβ and CD45RA depletion, respectively) haploidentical hematopoietic cell transplant (HCT) following reduced intensity conditioning regimen that avoids radiation in patients with hematologic malignancies that have relapsed or are refractory following prior allogeneic transplantation.

PRIMARY OBJECTIVE:

* To estimate engraftment by day +30 post-transplant in patients who receive TCRɑβ-depleted and CD45RA-depleted haploidentical donor progenitor cell transplantation following reduced intensity conditioning regimen without radiation.

SECONDARY OBJECTIVES:

* Assess the safety and feasibility of the addition of Blinatumomab in the early post-engraftment period in patients with CD19+ malignancy.
* Estimate the incidence of malignant relapse, event-free survival, and overall survival at one-year post-transplantation.
* Estimate incidence and severity of acute and chronic (GVHD).
* Estimate the rate of transplant related mortality (TRM) in the first 100 days after transplantation.

Conditions

• Acute Lymphoblastic Leukemia (ALL)
• Acute Myeloid Leukemia (AML)
• Myeloid Sarcoma
• Chronic Myeloid Leukemia (CML)
• Juvenile Myelomonocytic Leukemia (JMML)
• Myelodysplastic Syndrome (MDS)
• Non-Hodgkin Lymphoma (NHL)

Interventions

DRUG

Anti-thymocyte globulin (rabbit)

Given intravenous (IV) prior to transplant on Days -14, -13, -12.

DRUG

Blinatumomab

Given by continuous IV infusion at least 2 weeks post-engraftment. Blinatumomab will be given only to patients with CD19+ malignancies.

DRUG

Cyclophosphamide

Given by IV infusion prior to transplant on Day -9.

DRUG

Fludarabine

Given IV prior to transplant on Days -8, -7, -6, -5, and -4.

DRUG

G-CSF

Given IV or subcutaneous (SQ) following transplant on Days 6 and 7.

DRUG

Melphalan

Given IV prior to transplant on Days -2 and -1.

DRUG

Mesna

Given IV prior to cyclophosphamide administration and at approximately 3, 6, and 9 hours after cyclophosphamide infusion.

DRUG

Rituximab

Given IV prior to transplant on Day -1.

DRUG

Tacrolimus

Given oral (PO) or IV beginning prior to transplant on Day -2. The dose will begin to taper at approximately day +60 after transplant in the absence of GVHD. Tacrolimus was used for the first 5 participants enrolled on study. Subsequent participants receive sirolimus.

DRUG

Thiotepa

Given IV prior to transplant on Day -3.

BIOLOGICAL

HPC,A Infusion

Hematopoietic Progenitor Cell, Apheresis (HPC,A) infusion of TCRɑβ+ depleted cells on day of transplant (Day 0) and HPC,A infusion of CD45RA+ depleted cells on Day +1 following transplant.

DEVICE

CliniMACS

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, such as CD3+ human T cells.

DRUG

Sirolimus

Given orally (PO) starting Day 0. The dose will be tapered off over two weeks starting on Day +42 in the absence of GVHD.

Sponsors & Collaborators

• St. Jude Children's Research Hospital

  lead OTHER

Principal Investigators

• Brandon Triplett, MD · St. Jude Children's Research Hospital

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Max Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-07-14

Primary Completion

2025-07-01

Completion

2026-07-01

FDA Drug

Yes

FDA Device

Yes

Countries

• United States

Study Locations