A Phase 1, First in Human Study of Adoptive T Cell Therapy With T Cells Stimulated by Dendritic Cell (DC)/Tumor Fusions in Combination With Decitabine and Venetoclax in Patients With Acute Myeloid Leukemia (AML)
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)
• Patients must have AML at initial diagnosis for which decitabine/venetoclax is planned as standard of care therapy. This can include patients with IDH or FLT-3 mutations for whom the addition of targeted therapy agents directed at IDH or FLT-3 mutations to the decitabine/venetoclax regimen is preferred per the treating physician.
• Patients with AML in first relapse after cytotoxic and/or targeted therapy for which decitabine and venetoclax therapy is appropriate standard of care. This can include patients with IDH or FLT-3 mutations for whom the addition of targeted therapy agents directed at IDH or FLT-3 mutations to the decitabine/venetoclax regimen is preferred per the treating physician.
• ECOG performance status ≤ 2 (Appendix A)
• Participants must have normal organ and marrow function as defined below:
‣ total bilirubin≤ 2.0 mg/dL
⁃ AST/ALT ≤ 3 × institutional upper limit of normal
⁃ creatinine ≤ 2.0 mg/dl
• The effects of vaccine stimulated T cells on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Ability to understand and the willingness to sign a written informed consent document.
• Patients must have obtained a response of PR or better to decitabine and venetoclax as defined in Section 11.
• Resolution of all HMA/venetoclax related grade III-IV toxicity as per CTC criteria 4.0, other than grade 3 anemia.
• Laboratories:
‣ ANC ≥ 1,000/µL
⁃ Platelets ≥ 50,000/uL
⁃ Bilirubin ≤ 2.0 mg/dL
⁃ Creatinine ≤ 2.0 mg/dL
⁃ AST/ALT ≤ 3.0 x ULN
• Patient completed 4 cycles of decitabine and venetoclax without evidence of disease recurrence or progression
• Resolution of all chemotherapy related grade III-IV toxicity as per CTC criteria 4.0, other than grade 3 anemia, at the time of initiation of cycle 5, 6, or 7 of decitabine/venetoclax therapy.
• Laboratories:
‣ ANC ≥ 1,000/µL
⁃ Platelets ≥ 50,000/uL
⁃ Bilirubin ≤ 2.0 mg/dL
⁃ Creatinine ≤ 2.0 mg/dL
⁃ AST/ALT ≤ 3.0 x ULN
• Generation of adequate yield of T cells to meet dosing requirement