The goal of this research study is to test if the combination of a new T cell therapy (dendritic cell (DC) / acute myeloid leukemia (AML) primed T cells), vaccine (DC/AML fusion vaccine) and standard of care decitabine and venetoclax is feasible and safe and effective for treatment of acute myeloid leukemia (AML). The names of the study drugs involved in this study are: * DC/AML fusion vaccine (immune cell vaccine) * Granulocyte-macrophage colony-stimulating factor (GM-CSF) (a type of growth factor or hormone) * DC/AML Primed T cells (immune cells) * Decitabine (a type of chemotherapy drug) * Venetoclax (a type of antineoplastic agent)
The study is a dose escalation phase I clinical trial to evaluate the feasibility, safety, clinical and immune effects of adoptive T cell therapy with DC/AML Primed T cells in participants with acute myeloid leukemia (AML) treated with decitabine and venetoclax. The U.S. Food and Drug Administration (FDA) has not approved DC/AML Vaxprimed T cells as a treatment for any disease. This is the first time that DC/AML Primed T cells will be given to humans. The U.S. Food and Drug Administration (FDA) has not approved DC/AML fusion vaccine as a treatment for any disease. The U.S. Food and Drug Administration (FDA) has approved GM-CSF, decitabine and venetoclax as treatment options for acute myeloid leukemia (AML). It is expected that about 30 people will take part in this research study
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Autologous fusion vaccine of dendritic cells and AML cells, via subcutaneous injection (under the skin) per standard of care.
Autologous adoptive T cells, via intravenous (into the vein) infusion, per protocol.
A pyrimidine nucleoside analogue, via intravenous infusion, per standard of care.
A BCL-2 inhibitor, taken orally per standard of care.
A Granulocyte-Macrophage Colony-Stimulating Factor, via subcutaneous injection, per standard of care.
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
RECRUITINGSuccessful Manufacture and Administration Rate of Vaccine-Educated T Cells
Successful manufacture and administration rate is defined as the proportion of enrolled participants for whom autologous vaccine-educated T cells are successfully manufactured and administered per protocol.
Time frame: 28 weeks
Maximum Tolerated Dose (MTD) of Vaccine-Educated T Cells
The MTD is defined as the highest dose level that one or fewer participants experiences a dose-limiting toxicity (DLT) or one dose level below the maximum administered dose level where two or more participants experience a DLT.
Time frame: 56 Days
Toxicity Rate of Vaccine-Educated T Cells, Including CRS, Neurotoxicity, and Infections
Toxicity rate of vaccine-educated T cells is defined as the proportion of participants who experience at least one toxicity, including cytokine release syndrome, neurotoxicity, or infections, out of all participants who receive at least one T-cell infusion.
Time frame: 5 years
Relapse-Free Survival (RFS) at 1 Year Post Administration of Vaccine Educated T Cells
RFS based on Kaplan-Meier method is defined as the time from the first T-cell infusion to the first documented disease relapse or death from any cause. Participants without relapse will be censored at the last disease assessment. Relapse is defined as the reappearance of blasts in the blood, or a bone marrow aspirate and biopsy showing \>5% blasts, not attributable to another cause. If there are no circulating blasts, a repeat bone marrow performed \>1 week later documenting more than 5% blasts is necessary to meet criteria for relapse.
Time frame: 1 year
Relapse-Free Survival (RFS) at 2 Years Post Administration of Vaccine Educated T Cells
RFS based on Kaplan-Meier method is defined as the time from the first T-cell infusion to the first documented disease relapse or death from any cause. Participants without relapse will be censored at the last disease assessment. Relapse is defined as the reappearance of blasts in the blood, or a bone marrow aspirate and biopsy showing \>5% blasts, not attributable to another cause. If there are no circulating blasts, a repeat bone marrow performed \>1 week later documenting more than 5% blasts is necessary to meet criteria for relapse.
Time frame: 2 years
MRD Negative Conversion Rate
MRD negative conversion rate is defined as the proportion of participants who convert from MRD-positive status at baseline to MRD-negative status at a subsequent post-baseline assessment,
Time frame: MRD samples are collected up to 6 months after the last cell therapy dose.
Median Overall Survival (OS)
Overall survival (OS), estimated using the Kaplan-Meier method, is defined as the time from registration to death from any cause. Participants without a death event will be censored at the last date they are known to be alive.
Time frame: 5 years
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