Adoptive T Cell Therapy with Dendritic Cell/ AML (DC/AML) Fusion Vaccine with Decitabine and Venetoclax for the Treatment of Acute Myeloid Leukemia

Inclusion Criteria

• STEP 1 (PRIOR TO TUMOR COLLECTION): 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
• STEP 1 (PRIOR TO TUMOR COLLECTION): 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
• STEP 1 (PRIOR TO TUMOR COLLECTION): Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• STEP 1 (PRIOR TO TUMOR COLLECTION): Total bilirubin ≤ 2.0 mg/dL
• STEP 1 (PRIOR TO TUMOR COLLECTION): Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 × institutional upper limit of normal
• STEP 1 (PRIOR TO TUMOR COLLECTION): Creatinine ≤ 2.0 mg/dl
• STEP 1 (PRIOR TO TUMOR COLLECTION): 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
• STEP 1 (PRIOR TO TUMOR COLLECTION): Ability to understand and the willingness to sign a written informed consent document
• STEP 2 (PRIOR TO LEUKAPHERESIS): Patients must have obtained a response of partial response (PR) or better to decitabine and venetoclax
• STEP 2 (PRIOR TO LEUKAPHERESIS): Resolution of all hypomethylating agent (HMA)/venetoclax related grade III-IV toxicity as per common terminology criteria (CTC) criteria 4.0, other than grade 3 anemia
• STEP 2 (PRIOR TO LEUKAPHERESIS): Absolute neutrophil count (ANC) ≥ 1,000/µL
• STEP 2 (PRIOR TO LEUKAPHERESIS): Platelets ≥ 50,000/uL
• STEP 2 (PRIOR TO LEUKAPHERESIS): Bilirubin ≤ 2.0 mg/dL
• STEP 2 (PRIOR TO LEUKAPHERESIS): Creatinine ≤ 2.0 mg/dL
• STEP 2 (PRIOR TO LEUKAPHERESIS): AST/ALT ≤ 3.0 x upper limit of normal (ULN)
• STEP 3 (PRIOR TO TREATMENT WITH DC/AML PRIMED T CELLS AND DC/AML FUSION VACCINE): Patient completed 4 cycles of decitabine and venetoclax without evidence of disease recurrence or progression
• STEP 3 (PRIOR TO TREATMENT WITH DC/AML PRIMED T CELLS AND DC/AML FUSION VACCINE): 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
• STEP 3 (PRIOR TO TREATMENT WITH DC/AML PRIMED T CELLS AND DC/AML FUSION VACCINE): ANC ≥ 1,000/µL
• STEP 3 (PRIOR TO TREATMENT WITH DC/AML PRIMED T CELLS AND DC/AML FUSION VACCINE): Platelets ≥ 50,000/uL
• STEP 3 (PRIOR TO TREATMENT WITH DC/AML PRIMED T CELLS AND DC/AML FUSION VACCINE): Bilirubin ≤ 2.0 mg/dL
• STEP 3 (PRIOR TO TREATMENT WITH DC/AML PRIMED T CELLS AND DC/AML FUSION VACCINE): Creatinine ≤ 2.0 mg/dL
• STEP 3 (PRIOR TO TREATMENT WITH DC/AML PRIMED T CELLS AND DC/AML FUSION VACCINE): AST/ALT ≤ 3.0 x ULN
• STEP 3 (PRIOR TO TREATMENT WITH DC/AML PRIMED T CELLS AND DC/AML FUSION VACCINE): Generation of adequate yield of T cells to meet dosing requirement

Exclusion Criteria

• STEP 1 (PRIOR TO TUMOR COLLECTION): Patients diagnosed with acute promyelocytic leukemia
• STEP 1 (PRIOR TO TUMOR COLLECTION): Patients treated at initial diagnosis who are appropriate for intensive induction therapy
• STEP 1 (PRIOR TO TUMOR COLLECTION): Patients with active systemic autoimmune disease requiring ongoing systemic therapy are excluded. The following is an exception to this criterion: subjects with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement. Patients with paraneoplastic auto-immune manifestations related to AML are allowed
• STEP 1 (PRIOR TO TUMOR COLLECTION): Patients who have received a prior allogeneic transplant will be excluded
• STEP 1 (PRIOR TO TUMOR COLLECTION): Because of compromised cellular immunity, patients who have active human immunodeficiency virus (HIV), untreated hepatitis C virus (HCV) or evidence of active hepatitis B virus (HBV)
• STEP 1 (PRIOR TO TUMOR COLLECTION): Patients must not have active significant cardiac disease characterized by symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia
• STEP 1 (PRIOR TO TUMOR COLLECTION): Patients must not be pregnant. All premenopausal patients will undergo pregnancy testing. Men will agree to not father a child while on protocol treatment. Men and women will practice effective birth control while receiving protocol treatment
• STEP 2 (PRIOR TO LEUKAPHERESIS): Patients must not have serious intercurrent illness such as infection requiring IV antibiotics, or significant cardiac disease characterized by significant arrhythmia, ischemic coronary disease or congestive heart failure
• STEP 2 (PRIOR TO LEUKAPHERESIS): Patients who, with their treating physician, choose to proceed with an allogeneic transplant at the time of remission will not be eligible for leukapheresis
• STEP 2 (PRIOR TO LEUKAPHERESIS): Patients with active systemic autoimmune disease requiring ongoing systemic therapy are excluded. The following is an exception to this criterion: subjects with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement. Patients with paraneoplastic auto-immune manifestations related to AML are permitted
• STEP 2 (PRIOR TO LEUKAPHERESIS): Current or prior use of immunosuppressive medication within 14 days prior to first T cell infusion. The following are exceptions to this criterion: intranasal, inhaled, topical or local steroid injections (eg. intra-articular injection); steroids as premedication for hypersensitivity reactions; systemic corticosteroid at physiologic doses not to exceed 10mg/day of prednisone or equivalent
• STEP 2 (PRIOR TO LEUKAPHERESIS): Known human immunodeficiency virus (HIV), untreated hepatitis C virus (HCV) or evidence of active hepatitis B virus (HBV)
• STEP 2 (PRIOR TO LEUKAPHERESIS): Female subjects who are pregnant, breast-feeding or female patients of reproductive potential who are not employing an effective method of birth control from starting treatment, including dosing interruptions through 90 days after last dose of treatment. Refrain from egg cell donation while receiving vaccination and for at least 90 days after the last dose of treatment
• STEP 2 (PRIOR TO LEUKAPHERESIS): Male subjects who are not employing an effective method of birth control from starting vaccine, including dosing interruptions through 90 days after receipt of the last dose of treatment. Refrain from sperm cell donation while receiving vaccination and for at least 90 days after the last dose of treatment