Haploidentical Allogeneic Transplant With Post-transplant Infusion of Regulatory T-cells
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|ClinicalTrials.gov Identifier: NCT01050764|
Recruitment Status : Terminated (Safety)
First Posted : January 15, 2010
Results First Posted : May 11, 2017
Last Update Posted : June 27, 2018
|Condition or disease||Intervention/treatment||Phase|
|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)||Drug: Regulatory T-cells Drug: Conventional T-cells Drug: Melphalan Drug: Thiotepa Device: Fludarabine Drug: Anti-thymocyte globulin, rabbit Drug: CliniMACS CD34 Reagent System||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Study Start Date :||June 2009|
|Actual Primary Completion Date :||August 2012|
|Actual Study Completion Date :||June 2014|
|Experimental: T-reg Cell Infusion after Allogeneic Stem Cell Transplant||
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:
Other Name: T-reg cells
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.
Other Name: T-con cells
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)
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)
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.
- Maximum-tolerated Dose (MTD) of Regulatory and Conventional T-cells [ Time Frame: 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).
- Acute Graft-versus-Host-Disease (aGvHD) [ Time Frame: 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.
- Overall Survival (OS), 1 Year [ Time Frame: 1 year ]Assessed as subjects remaining alive 12 months after CD34+ cell infusion (ie, excludes death due to any cause)
- Median Overall Survival (OS) [ Time Frame: 25 months ]Reported as the median overall survival (OS) in months from infusion of the hematopoietic stem cells (HSCT)
- To Measure the Incidence and Severity of Acute and Chronic GvHD [ Time Frame: 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)
- Serious Infections [ Time Frame: 1 year ]Serious infections are reported as the number of participants experienced serious infections.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01050764
|United States, California|
|Stanford University School of Medicine|
|Stanford, California, United States, 94305|
|Principal Investigator:||Everett H Meyer, MD, PhD||Stanford University|