Partially HLA Mismatched (Haploidentical) Allogeneic Bone Marrow Transplantation

Summary

Allogeneic stem cell transplantation is a potentially curative treatment for patients with many hematologic malignancies (e.g. leukemia, lymphoma, and myeloma with high risk of relapse). This process requires a suitable donor. The best case scenario involves an Human Leukocyte Antigen (HLA) matched sibling donor. However, this type of donor is not always available. Donor registries can provide another source for matched unrelated donors, but this may take valuable time delaying treatment for the transplant recipient. Donor availability remains a significant barrier to the use of allogeneic (from a donor) stem cell transplant. This issue disproportionately affects patients of minority backgrounds. Novel strategies to improve outcomes using alternative donors are desperately needed.

Haploidentical transplants are an alternative which provides a readily available donor in the form of a partially HLA matched family member. This provides for more potential donors and the donors can be selected based on other factors that can play a role in transplant success (e.g. age, gender, KIR alloreactivity). Recent advances in transplant techniques have greatly improved success rates with haploidentical transplants although disease relapse has remained as issue.

This trial aims to provide an alternative transplant option for patients with hematologic malignancies who require bone marrow transplantation but lack an HLA identical donor. The investigational component of this study is the combination of the Fludarabine/ Busulfan/ Total Body Irradiation conditioning regimen and the HLA Haploidentical Transplant with post-transplant Cyclophosphamide.

Conditions

• Hematologic Malignancies

Interventions

PROCEDURE

Haploidentical Transplant

Subjects will be dosed with pre-transplant Fludarabine (180mg/m2)and Busulfan total AUC 2400 μmol\*min/L or 6.4mg/kg. Subjects will then undergo total body irradiation 2Gy. Subjects will undergo haploidentical allogeneic bone marrow transplant, followed by Cyclophosphamide, Tacrolimus and MMF based GVHD prophylaxis.

DRUG

Fludarabine

Subjects in this trial will receive Fludarabine 30 mg/m2 IV QD, adjusted for CrCl from Days -8 through -3.

DRUG

Busulfan

Subjects in this trial will receive Busulfan total AUC 2400 μmol\*min/L or 6.4mg/kg in 4 doses with seizure prophylaxis from Days -6 through -3.

RADIATION

Total Body Irradiation

Subjects in this trial will receive total body irradiation (2Gy fractionated) from Day -2 or -1.

DRUG

Cyclophosphamide

Subjects in this trial will receive Cyclophosphamide 50 mg/kg IV QD on Days 3 and 4 post-transplant.

Sponsors & Collaborators

• University of Illinois at Chicago

  lead OTHER

Principal Investigators

• Pritesh Patel, MD · University of Illinois at Chicago

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

10 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-08-30

Primary Completion

2014-05-15

Completion

2014-05-15

Countries

• United States

Study Locations