Gamma delta T-cells are part of the innate immune system with the ability to recognize malignant cells and kill them. This study uses gamma delta T-cells to maximize the anti-tumor response and minimize graft versus host disease (GVHD) in leukemic and myelodysplastic patients who have had a partially mismatched bone marrow transplant (haploidentical).
Many patients with hematological malignancies require a bone marrow transplant for curative treatment. A matched sibling donor is optimal but may not be available. Therefore, a partially matched family member (haploidentical) may be a viable alternative. The incidence of graft vs. host disease, however, can become more of a significant, even fatal, factor with partial matches. T-cells have been shown to be the key player in the post-transplant immune phenomena. The majority of T-cells are composed of alpha beta T-cells with a small minority of gamma delta T-cells, which are known to have the unique ability to kill malignant cells without antigen recognition. This study proposes to extract, concentrate, and activate gamma delta T-cells from the peripheral blood to provide innate anti-tumor effect with minimal risk of GVHD. Safety and impact and/or the rate of GVHD will be evaluated.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
38
The Alpha Beta (α/β) T-Cell Depletion System utilizes the CliniMACS instrument to yield a gamma delta (γδ) enriched cell therapy product.
The Alpha Beta (α/β) T-Cell Depletion System utilizes the CliniMACS instrument to yield a gamma delta (γδ) enriched cell therapy product.
University of Kansas Cancer Center
Westwood, Kansas, United States
RECRUITINGOhio State University Medical Center
Columbus, Ohio, United States
RECRUITINGPhase I - Dose-limiting toxicity (DLT)
The dose escalation strategy will follow the Food and Drug Administration Guideline for design of early phase clinical trials of cellular therapy products.
Time frame: Baseline to Day 30
Phase I - Severe acute adverse events following infusion of EAGD T-cells
Safety of the infusion will be based on the risk of treatment-related severe adverse events as identified in the National Cancer Common Terminology Criteria for Adverse Events (CTCAE) version 4.
Time frame: Baseline to Day 100
Expansion phase - Rate of acute GVHD
Monitoring for GVHD is assessed with Grade II-IV adverse events as identified by the National Cancer Common Terminology Criteria for Adverse Events (CTCAE) version 4.
Time frame: Baseline to Day 100
Expansion phase - Relapse following haploidentical HCT and PTCy with EAGD T-cell infusion
Number of subjects who have acute GVHD by day 100 post-HCT after infusion of EAGD T-cells
Time frame: Baseline to 100 days
Expansion phase - Non-relapse mortality following haploidentical HCT and PTCy with EAGD T-cell infusion
Number of subjects who have no relapse by day 100 post-HCT after infusion
Time frame: Baseline to 100 days
Expansion phase - Overall survival following haploidentical HCT and PTCy with EAGD T-cell infusion
Number of subjects who are living by day 100 post-HCT after infusion
Time frame: Baseline to 100 days
Rate of one-year relapse-free survival (RFS)
Number of subjects living without relapse of disease after one year following HCT
Time frame: Baseline to one year
Rate of one-year non-relapse mortality (NRM)
Number of subjects no longer living but not from disease relapse after one year following HCT
Time frame: Baseline to one year
Rate of one-year overall survival (OS)
Number of subjects living after one year following HCT
Time frame: Baseline to one year
Proportion of subjects with chronic GVHD at one year
Number of subjects with chronic GVHD after one year following HCT
Time frame: Baseline to one year
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