NCT01050764

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

A Feasibility Trial of Post-Transplant Infusion of Allogeneic Regulatory T Cells and Allogeneic Conventional T Cells in Patients With Hematologic Malignancies Undergoing Allogeneic Myeloablative Hematopoietic Cell Transplantation From Haploidentical-Related Donors

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 10 (actual)
• Sponsor: Everett Meyer · Academic / Other
• Sex: All
• Age: 60 Years
• Healthy volunteers: Not accepted

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).

Detailed description

This is dose-escalation study intended to evaluate the use of classification determinant 15-positive (CD15+), CD4+, CD127dim, and FoxP3+ regulatory T-cells (T-reg cells) supplemented by conventional T-cells (T-con cells), to enhance the efficacy of allogeneic (CliniMACS CD34+ selected) hematopoietic stem cell transplantation (allo-HSCT), in the setting of leukemia, lymphoma, and myelodysplastic syndrome (MDS). This study investigates amelioration of the impaired immune recovery and address the significant relapse incidence in the haploidentical HSCT setting. Pre-transplant myeloablative conditioning will be melphalan; thiotepa; fludarabine and rabbit antithymocyte globulin (rATG). Stem cell rescue will be with CD34+ selected cells. The rescue infusion will be supplemented with infusions of regulatory T-cells (T-reg) and conventional T-cells (T-con) from the same donor collection, on Treatment Days 14 and 16 respectively. CD34+ cell infusion day is Treatment Day 0. T-reg cells are those cells enriched by immunomagnetic selection of CD25+ cells, and further purified by flow cytometric cell sorting for the CD15+, CD4+, CD127dim, FoxP3+ cell population. These cells are an enriched but naturally-occurring T-cell population. T-con cells are unseparated/unfractionated cells, ie, as collected by the peripheral blood stem cells apheresis procedure. Post-transplant follow-up is for 5 years.

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

Type	Name	Description
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.

Timeline

• Start date: 2009-06-01
• Primary completion: 2012-08-01
• Completion: 2014-06-01
• First posted: 2010-01-15
• Last updated: 2018-06-27
• Results posted: 2017-05-11

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study