Clinical trial NCT01050764
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)
Sponsor: Everett Meyer
Start date: 2009-06-01; Completion date: 2014-06-01
Enrollment: 10 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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.

Arms: arm 1: None
Interventions: intervention 1: Regulatory T-cells intervention 2: Conventional T-cells intervention 3: Melphalan intervention 4: Thiotepa intervention 5: Fludarabine intervention 6: Anti-thymocyte globulin, rabbit intervention 7: CliniMACS CD34 Reagent System
Intervention descriptions: intervention 1: 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 intervention 2: 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. intervention 3: 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) intervention 4: 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) intervention 5: 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 intervention 6: 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 intervention 7: 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.

Protocol documents: