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

Phase 1

Terminated

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

Interventions: Drug: Regulatory T-cells
Drug: Conventional T-cells
Drug: Melphalan
Drug: Thiotepa
Device: Fludarabine
Drug: Anti-thymocyte globulin, rabbit
Drug: CliniMACS CD34 Reagent System

Brief 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.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
T-reg Cell Infusion after Allogeneic Stem Cell Transplant	Conventional T-cells	-
T-reg Cell Infusion after Allogeneic Stem Cell Transplant	CliniMACS CD34 Reagent System	-
T-reg Cell Infusion after Allogeneic Stem Cell Transplant	Anti-thymocyte globulin, rabbit	-
T-reg Cell Infusion after Allogeneic Stem Cell Transplant	Regulatory T-cells	-
T-reg Cell Infusion after Allogeneic Stem Cell Transplant	Fludarabine	-
T-reg Cell Infusion after Allogeneic Stem Cell Transplant	Melphalan	-
T-reg Cell Infusion after Allogeneic Stem Cell Transplant	Thiotepa	-

Primary Outcome Measures

Name	Time	Method
Maximum-tolerated Dose (MTD) of Regulatory and Conventional T-cells	30 days after HSCT infusion	The maximum-tolerated dose (MTD) was to be determined based on the safety and feasibility observed for a pre-determined set of cellular dose level combinations of regulatory T-cells (T-reg) and conventional T-cells (T-con).

Secondary Outcome Measures

Name	Time	Method
To Measure the Incidence and Severity of Acute and Chronic GvHD	1 year	Population of participants that received HSCT and T-reg plus T-con, and developed actue, chronic, or any graft vs host disease (GvHD)
Overall Survival (OS), 1 Year	1 year	Assessed as subjects remaining alive 12 months after CD34+ cell infusion (ie, excludes death due to any cause)
Median Overall Survival (OS)	25 months	Reported as the median overall survival (OS) in months from infusion of the hematopoietic stem cells (HSCT)
Serious Infections	1 year	Serious infections are reported as the number of participants experienced serious infections.
Acute Graft-versus-Host-Disease (aGvHD)	1 year	The primary outcome was incidence of grade 3 or 4 acute graft-vs-host-disease (aGvHD), reported as the number of participants developing grade 3 or 4 aGvHD.