Vaccine Therapy in Treating Patients with Acute Myeloid Leukemia following Chemotherapy-Induced Remission

Inclusion Criteria

• STEP 1: INCLUSION CRITERIA FOR TUMOR COLLECTION
• Patients must have AML at initial diagnosis or at first relapse
• Patients must be >= 55 years old
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Total bilirubin =< 2.0 mg/dL
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional upper limit of normal
• Creatinine =< 2.0 mg/dl
• The effects of DC/AML fusion 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
• STEP 2: INCLUSION CRITERIA PRIOR TO RANDOMIZATION
• Patients must have obtained a complete remission with chemotherapy defined by the absence of circulating blasts, and less than 5% blasts on bone marrow examination following hematopoietic recovery
• Patient required no more than 2 cycles of chemotherapy or 4 cycles of a hypomethylating agent (alone or in conjunction with venetoclax) to achieve remission
• Resolution of all chemotherapy related grade III-IV toxicity as per Common Toxicity Criteria (CTC) criteria 4.0
• Absolute neutrophil count (ANC) >= 1,000/uL
• Platelets >= 50,000/uL
• Bilirubin =< 2.0 mg/dL
• Creatinine =< 2.0 mg/dL
• AST/ALT =< 3.0 x upper limit of normal (ULN)
• For patients with evidence of minimal residual disease prior to vaccination, assessment of minimal residual disease status by cytogenetics or fluorescence in situ hybridization (FISH) will be followed post vaccination
• STEP 3: ELIGIBILITY CRITERIA PRIOR TO TREATMENT OR OBSERVATION
• Resolution of all chemotherapy related grade III-IV toxicity as per CTC criteria 4.0
• White blood cells (WBC) >= 2.0 X 10^3/uL
• Platelet >= 50,000/uL
• Bilirubin =< 2.0 mg/ dL
• Creatinine =< 2.0 mg/ dL
• AST/ALT =< 3.0 x ULN
• At least 2 doses of fusion vaccine were produced (Arm A only)
• INCLUSION CRITERIA FOR PATIENTS PREVIOUSLY ENROLLED ON PROTOCOL 18-232
• STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: Patients must have AML in first or second remission
• STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: Patients must have previously had leukemia tumor cells collected and cryopreserved as outlined in the (Dana-Farber Harvard Cancer Center) DF/HCC tumor collection protocol 18-232
• STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: Patients must be >= 55 years old
• STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: ECOG performance status =< 2
• STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: Total bilirubin =< 2.0 mg/dL
• STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: AST(SGOT)/ALT(SGPT) =< 3 x institutional upper limit of normal
• STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: Creatinine =< 2.0 mg/dl
• STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: ANC >= 1,000/uL
• STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: Platelets >= 50,000/uL
• STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: The effects of DC/AML fusion 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 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: Ability to understand and the willingness to sign a written informed consent document
• STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: Patients must have obtained a complete remission with chemotherapy defined by the absence of circulating blasts, and less than 5% blasts on bone marrow examination following hematopoietic recovery
• STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: Patient required no more than 2 cycles of chemotherapy or 4 cycles of a hypomethylating agent (alone or in conjunction with venetoclax) to achieve remission
• STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: Resolution of all chemotherapy related grade III-IV toxicity as per CTC criteria 4.0
• STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: For patients with evidence of minimal residual disease prior to vaccination, assessment of minimal residual disease status by cytogenetics or FISH will be followed post vaccination
• STEP 3: ELIGIBILITY CRITERIA PRIOR TO TREATMENT OR OBSERVATION: Resolution of all chemotherapy related grade III-IV toxicity as per CTC criteria 4.0
• STEP 3: ELIGIBILITY CRITERIA PRIOR TO TREATMENT OR OBSERVATION: WBC >= 2.0 X 10^3/uL
• STEP 3: ELIGIBILITY CRITERIA PRIOR TO TREATMENT OR OBSERVATION: Platelets >= 50,000/uL
• STEP 3: ELIGIBILITY CRITERIA PRIOR TO TREATMENT OR OBSERVATION: Bilirubin =< 2.0 mg/dL
• STEP 3: ELIGIBILITY CRITERIA PRIOR TO TREATMENT OR OBSERVATION: Creatinine =< 2.0 mg/dL
• STEP 3: ELIGIBILITY CRITERIA PRIOR TO TREATMENT OR OBSERVATION: AST/ALT =< 3.0 x ULN
• STEP 3: ELIGIBILITY CRITERIA PRIOR TO TREATMENT OR OBSERVATION: At least 2 doses of fusion vaccine were produced (Arm A only)

Exclusion Criteria

• STEP 1: EXCLUSION CRITERIA FOR 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 permitted
• Patients who have received a prior allogeneic transplant will be excluded
• Because of compromised cellular immunity, patients who have a known human immunodeficiency virus (HIV), untreated hepatitis C virus (HCV) or evidence of active hepatitis B virus (HBV)
• Patients must not have active significant cardiac disease characterized by symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia
• 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
• Patients with prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ will be excluded; cancer treated with curative intent within 5 years of enrollment, with low risk of recurrence, will be allowed following approval by the principal investigator; cancer treated with curative intent > 5 years prior to enrollment is allowed
• STEP 2: EXCLUSION CRITERIA PRIOR TO RANDOMIZATION
• 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
• Patients who, with their treating physician, choose to proceed with an allogeneic transplant at the time of remission will not be eligible for randomization
• Patients with active systemic autoimmune disease requiring ongoing systemic therapy are excluded. The following is an exception to this criterion: subjects with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement. Patients with paraneoplastic auto-immune manifestations related to AML are permitted
• Current or prior use of immunosuppressive medication within 14 days prior to first vaccine; the following are exceptions to this criterion: intranasal, inhaled, topical or local steroid injections (e.g. intra-articular injection); steroids as premedication for hypersensitivity reactions; systemic corticosteroid at physiologic doses not to exceed 10 mg/day of prednisone or equivalent
• Known human immunodeficiency virus (HIV), hepatitis C virus (HCV) or evidence of active hepatitis B virus (HBV)
• Receipt of live attenuated vaccination within 30 days prior to the first vaccine
• 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 vaccine, including dosing interruptions through 90 days after receipt of the last vaccine; refrain from egg cell donation while receiving vaccination and for at least 90 days after the last vaccine
• 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 vaccine; refrain from sperm cell donation while receiving vaccination and for at least 90 days after the last vaccine
• EXCLUSION CRITERIA FOR PATIENTS PREVIOUSLY ENROLLED ON PROTOCOL 18-232
• STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: Patients with active systemic autoimmune disease requiring ongoing systemic therapy are excluded. The following is an exception to this criterion: subjects with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement. Patients with paraneoplastic auto-immune manifestations related to AML are permitted
• STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: Patients who have received a prior allogeneic transplant will be excluded
• STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: Because of compromised cellular immunity, patients who have a known human immunodeficiency virus (HIV), hepatitis C virus (HCV) or evidence of active hepatitis B virus (HBV)
• STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: Patients must not have active significant cardiac disease characterized by symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia
• STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: 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 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: Patients with prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ will be excluded. Cancer treated with curative intent within 5 years of enrollment, with low risk of recurrence, will be allowed following approval by the principal investigator. Cancer treated with curative intent > 5 years prior to enrollment is allowed
• STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: Patients must not have serious intercurrent illness such as infection requiring intravenous (IV) antibiotics, or significant cardiac disease characterized by significant arrhythmia, ischemic coronary disease or congestive heart failure
• STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: Patients who, with their treating physician, choose to proceed with an allogeneic transplant at the time of remission will not be eligible for randomization
• STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: Current or prior use of immunosuppressive medication within 14 days prior to first vaccine; 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 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: Receipt of live attenuated vaccination within 30 days prior to the first vaccine
• STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: 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 vaccine, including dosing interruptions through 90 days after receipt of the last vaccine; refrain from egg cell donation while receiving vaccination and for at least 90 days after the last vaccine
• STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: 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 vaccine; refrain from sperm cell donation while receiving vaccination and for at least 90 days after the last vaccine