Phase I Study of Ex Vivo Expanded/Activated Gamma Delta T-cell Infusion Following Haploidentical Hematopoietic Stem Cell Transplantation and Post-transplant Cyclophosphamide
Summary
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).
Detailed description
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.
Arms & interventions
- DrugEAGD T-cell infusion (Phase I)
The Alpha Beta (α/β) T-Cell Depletion System utilizes the CliniMACS instrument to yield a gamma delta (γδ) enriched cell therapy product.
- DrugEAGD T-cell infusion (Expansion)
The Alpha Beta (α/β) T-Cell Depletion System utilizes the CliniMACS instrument to yield a gamma delta (γδ) enriched cell therapy product.
Outcome measures
Primary
Phase 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
Secondary
Expansion phase - Relapse following haploidentical HCT and PTCy with EAGD T-cell infusion
Time frame: Baseline to 100 days
Expansion phase - Non-relapse mortality following haploidentical HCT and PTCy with EAGD T-cell infusion
Time frame: Baseline to 100 days
Expansion phase - Overall survival following haploidentical HCT and PTCy with EAGD T-cell infusion
Time frame: Baseline to 100 days
Rate of one-year relapse-free survival (RFS)
Time frame: Baseline to one year
Rate of one-year non-relapse mortality (NRM)
Time frame: Baseline to one year
Rate of one-year overall survival (OS)
Time frame: Baseline to one year
Proportion of subjects with chronic GVHD at one year
Time frame: Baseline to one year
Eligibility criteria
Study locations (2)
University of Kansas Cancer Center
Westwood, Kansas, 66205
Ohio State University Medical Center
Columbus, Ohio, 43210-1238