Haploidentical Allogeneic Transplant With Post-transplant Infusion of Regulatory T-cells

Summary

Patients with hematologic malignancies will receive myeloablative chemotherapy followed by stem cell rescue with bone marrow or hematopoietic peripheral blood stem cells collected by apheresis from a filgrastim- (G-CSF)-mobilized haploidentical related-donor, ie, hematopoietic peripheral blood stem cell transplant (HSCT).

Conditions

• Leukemia, Acute
• Chronic Myelogenous Leukemia (CML)
• Myelodysplastic Syndrome (MDS)
• Non-Hodgkin Lymphoma (NHL)
• Chronic Lymphocytic Leukemia (CLL)
• Acute Myelogenous Leukemia (AML)
• Acute Lymphoblastic Leukemia (ALL)

Interventions

DRUG

Regulatory T-cells

To ameliorate the impaired immune recovery and address the significant relapse incidence in the haploidentical setting. Cells will be selected by a tandem selection process and infused on day +14. These are the enriched but naturally-occurring regulatory T cells. Possible dose cohorts and levels are: Cohort 1 * T-reg: 1 x 10e5/kg * T-con: 3 x10e5/kg Cohort 2 * T-reg: 3 x 10e5/kg * T-con: 1 x 10e6/kg Cohort 3 * T-reg: 1 x 10e6/kg * T-con: 3 x 10e6/kg Cohort 4 * T-reg: 3 x 10e6/kg * T-con: 1 x 10e7/kg

DRUG

Conventional T-cells

These are conventional (unselected) donor T-cells. Cell dosage of the infusion will be based on the CD3+ cell content and infused on day +16.

DRUG

Melphalan

Anti-cancer chemotherapy drug administered IV at 140 mg/m² on Day -8 prior to HSCT (a component of the conditioning regiment prior to infusion of cells)

DRUG

Thiotepa

Anti-cancer chemotherapy drug administered IV at 10 mg/kg on Day -7 prior to HSCT (a component of the conditioning regiment prior to infusion of cells)

DEVICE

Fludarabine

Anti-cancer chemotherapy drug administered IV at 160mg/m² on Days -6; -5; -4; and -3 prior to HSCT (a component of the conditioning regiment prior to infusion of cells

DRUG

Anti-thymocyte globulin, rabbit

Rabbit-derived antibodies against human T-cells used as transplant rejection prophylaxis. Administered at 6 mg/kg IV on Days -6; -5; -4; and -3 prior to HSCT

DRUG

CliniMACS CD34 Reagent System

An in vitro medical device system that uses antibodies conjugated to magnetic beads to select and enrich for CD34+ blood stem cells from the allogeneic donor apheresis product prior to HSCT, while removing other cells that can cause GvHD. CD34+ cell dosage will be based on the participant's body weight.

Sponsors & Collaborators

• Doris Duke Charitable Foundation

  collaborator OTHER

• Everett Meyer

  lead OTHER

Principal Investigators

• Everett H Meyer, MD, PhD · Stanford University

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Max Age

60 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2009-06-30

Primary Completion

2012-08-31

Completion

2014-06-30

FDA Drug

Yes

Countries

• United States

Study Locations