Haploidentical Donor Hematopoietic Progenitor Cell and NK Cell Transplantation for Hematologic Malignancy

Summary

In this study, participants with high-risk hematologic malignancies undergoing hematopoietic cell transplantation (HCT), who do not have a suitable human leukocyte antigen (HLA) matched related/sibling donor (MSD) or matched unrelated donor (MUD) identified, will receive a haploidentical donor HCT with additional natural killer (NK) cells.

The investigators anticipate enrollment of 75 donors and 75 recipients.

PRIMARY OBJECTIVE:

* To estimate the rate of successful engraftment at day +42 post-transplant in patients who receive haploidentical donor stem cell plus NK cell transplantation with TLI based conditioning regimen for high risk hematologic malignancy.

SECONDARY OBJECTIVES:

* 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

• Leukemia
• Lymphoma

Interventions

RADIATION

Total Lymphoid Irradiation

Participants receive total lymphoid irradiation over four doses.

DRUG

Fludarabine

Given IV.

DRUG

Cyclophosphamide

Given IV.

DRUG

Thiotepa

Given IV.

DRUG

Melphalan

Given IV.

BIOLOGICAL

HPC,A Infusion

Participants received infusions of HPC,A (CD34+ selected) and HPC,A (CD45RA depleted).

BIOLOGICAL

TC-NK Infusion

Participants receive infusions of TC-NK.

BIOLOGICAL

G-CSF

Participants receive G-CSF subcutaneously or intravenously. Donors receive G-CSF subcutaneously during cell mobilization.

DRUG

Mesna

Mesna is generally dosed at approximately 25% of the cyclophosphamide dose. It is generally given intravenously prior to and again at 3, 6 and 9 hours following each dose of cyclophosphamide.

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

Mycophenolate mofetil

Given intravenously or orally.

Sponsors & Collaborators

• Assisi Foundation

  collaborator OTHER

• St. Jude Children's Research Hospital

  lead OTHER

Principal Investigators

• Brandon M. 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

2013-05-16

Primary Completion

2021-08-27

Completion

2021-09-27

FDA Drug

Yes

FDA Device

Yes

Countries

• United States

Study Locations