Combined T Cell Depleted Haploidentical Peripheral Blood Stem Cell and Unrelated Umbilical Cord Blood Transplantation in Patients With Hematologic Malignancies Using a Total Lymphoid Irradiation Based Preparative Regimen

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), matched unrelated donor (MURD) or killer-immunoglobulin receptors (KIR) ligand mismatched haploidentical donor identified, will receive a combined T cell depleted (TCD) haploidentical peripheral blood stem cell (PBSC) and unrelated umbilical cord blood transplantation (UCBT) using a total lymphoid irradiation (TLI) based preparative regimen.

Primary objective:

* To estimate the incidence of donor derived neutrophil engraftment by day +42 post-transplant for participants with high-risk hematologic malignancies undergoing a total lymphoid irradiation (TLI)-based hematopoietic cell transplantation (HCT) using a T cell depleted (TCI) haploidentical donor peripheral blood stem cell (PBSC) donor combined with an unrelated umbilical cord blood (UCB) donor.

Secondary objectives:

* Estimate the incidence of malignant relapse, event-free survival (EFS), and overall survival (OS) at one-year post-transplantation.
* Estimate the incidence and severity of acute and chronic graft versus host disease (GVHD) in the first 100 days after transplantation.
* Estimate the incidence of secondary graft failure transplant related mortality (TRM) and transplant related morbidity in the first 100 days after HCT.

Conditions

• Hematological Malignancies

Interventions

DRUG

Cyclophosphamide

Given by intravenous infusion as part of the preparative regimen.

DRUG

Thiotepa

Given by intravenous infusion as part of the preparative regimen.

DRUG

Fludarabine

Given by intravenous infusion as part of the preparative regimen.

DRUG

Melphalan

Given by intravenous infusion as part of the preparative regimen.

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.

BIOLOGICAL

G-CSF

Given either by intravenous infusion or subcutaneously daily until absolute neutrophil count (ANC) \>2000 for 3 consecutive days.

DRUG

Mycophenolate mofetil

Given either orally or by intravenous infusion as part of the post-transplantation immunosuppression.

DRUG

Tacrolimus

Given either orally or by intravenous infusion as part of the post-transplantation immunosuppression.

DRUG

Methylprednisolone

Given either intravenously or orally, if needed to treat graft-versus-host-disease (GVHD).

RADIATION

Total lymphoid irradiation

TLI will be administered in divided fractions given at a minimum of 6 hours apart.

BIOLOGICAL

Lymphocyte infusions

Donors will undergo haploidentical mobilization with G-CSF. Cells will be collected by leukapheresis over two days, then processed using the investigational CliniMACS device and CD34 Microbead reagent as directed by the manufacturer.

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.

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

2014-07-11

Primary Completion

2017-05-23

Completion

2017-05-23

FDA Drug

Yes

FDA Device

Yes

Countries

• United States

Study Locations