Mismatched Family Member Donor Transplantation for Children and Young Adults With High Risk Hematological Malignancies

Summary

Blood and marrow stem cell transplant has improved the outcome for patients with high-risk hematologic malignancies. However, most patients do not have an appropriate HLA (immune type) matched sibling donor available and/or are unable to identify an acceptable unrelated HLA matched donor through the registries in a timely manner. Another option is haploidentical transplant using a partially matched family member donor.

Although haploidentical transplant has proven curative in many patients, this procedure has been hindered by significant complications, primarily regimen-related toxicity including GVHD and infection due to delayed immune reconstitution. These can, in part, be due to certain white blood cells in the graft called T cells. GVHD happens when the donor T cells recognize the body tissues of the patient (the host) are different and attack these cells. Although too many T cells increase the possibility of GVHD, too few may cause the recipient's immune system to reconstitute slowly or the graft to fail to grow, leaving the patient at high-risk for significant infection.

For these reasons, a primary focus for researchers is to engineer the graft to provide a T cell dose that will reduce the risk for GVHD, yet provide a sufficient number of cells to facilitate immune reconstitution and graft integrity. Building on prior institutional trials, this study will provide patients with a haploidentical (HAPLO) graft engineered to specific T cell target values using the CliniMACS system. A reduced intensity, preparative regimen will be used in an effort to reduce regimen-related toxicity and mortality.

The primary aim of the study is to help improve overall survival with haploidentical stem cell transplant in this high risk patient population by 1) limiting the complication of graft versus host disease (GVHD), 2) enhancing post-transplant immune reconstitution, and 3) reducing non-relapse mortality.

Conditions

• Leukemia, Acute Lymphocytic (ALL)
• Leukemia, Myeloid, Acute(AML)
• Leukemia, Myeloid, Chronic(CML)
• Juvenile Myelomonocytic Leukemia (JMML)
• Hemoglobinuria, Paroxysmal Nocturnal (PNH)
• Hodgkin Lymphoma
• Lymphoma, Non-Hodgkin (NHL)
• Myelodysplastic Syndrome (MDS)

Interventions

DEVICE

CliniMACS

Miltenyi Biotec CliniMACS stem cell selection device

PROCEDURE

Stem cell transplantation

An infusion of HLA mismatched family member donor stem cells processed through the use of the investigational Miltenyi Biotec CliniMACS device.

DRUG

Fludarabine

Transplant recipients will receive a conditioning regimen consisting of systemic chemotherapy and antibodies.

DRUG

Thioplex®

Transplant recipients will receive a conditioning regimen consisting of systemic chemotherapy and antibodies.

DRUG

L-phenylalanine mustard

Transplant recipients will receive a conditioning regimen consisting of systemic chemotherapy and antibodies.

DRUG

Mycophenolate mofetil

Transplant recipients will receive a conditioning regimen consisting of systemic chemotherapy and antibodies.

DRUG

Rituxan™

Transplant recipients will receive a conditioning regimen consisting of systemic chemotherapy and antibodies.

DRUG

Alemtuzumab

After January 2010, due to the unavailability of muromonab, transplant recipients received a conditioning regimen consisting of systemic chemotherapy and antibodies, including alemtuzumab.

DRUG

Cyclophosphamide

Transplant recipients will receive a conditioning regimen consisting of systemic chemotherapy and antibodies.

DRUG

Anti-thymocyte globulin (Rabbit)

Transplant recipients will receive a conditioning regimen consisting of systemic chemotherapy and antibodies.

DRUG

G-CSF

Transplant recipients will receive a conditioning regimen consisting of systemic chemotherapy and antibodies.

DRUG

Muromonab

Prior to January 2010, transplant participants received a conditioning regimen consisting of systemic chemotherapy and antibodies, including muromonab. Muromonab became unavailable from the manufacturer at that time and was replaced by alemtuzumab.

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

2007-12-14

Primary Completion

2016-01-27

Completion

2020-02-06

Countries

• United States

Study Locations