Summary

This randomized phase II trial studies how well vaccine therapy works in treating patients with acute myeloid leukemia following chemotherapy-induced remission. Vaccines made from a person's tumor cells may help the body build an effective immune response to kill tumor cells that express acute myeloid antigen.

Objectives

PRIMARY OBJECTIVE:
I. To assess the impact of therapy on 2-year progression free survival. (Clinical)

SECONDARY OBJECTIVES:
I. To assess the impact of therapy on overall survival. (Clinical)
II. To assess the toxicity associated with treating acute myeloid leukemia (AML) patients who are in remission with dendritic cell (DC)/AML fusion cells. (Clinical)
III. To assess the effect of vaccination with DC/AML fusions on the expansion of leukemia specific T cells. (Correlative)
IV. To determine immunologic response to neoantigens arising from patient specific mutational events. (Correlative)

OUTLINE: Patients who achieve complete remission after 1-2 courses of induction chemotherapy or up to 4 cycles of hypomethylating agents (alone or in conjunction with venetoclax) as standard of care, are randomized to 1 of 2 arms.

ARM A: Beginning 4-8 weeks after completing standard of care post-remission chemotherapy, patients receive allogeneic AML antigen-expressing dendritic cell vaccine subcutaneously (SC) and sargramostim SC in weeks 1, 5, and 9.

ARM C: Beginning 4-8 weeks after completing standard of care post-remission chemotherapy, patients undergo observation.

After completion of study treatment, patients are followed up monthly for 6 months, at 12 months, and then every 6 months for 5 years.

Eligibility

1. STEP 1: INCLUSION CRITERIA FOR TUMOR COLLECTION
2. Patients must have AML at initial diagnosis or at first relapse
3. Patients must be >= 55 years old
4. Eastern Cooperative Oncology Group (ECOG) performance status =< 2
5. Total bilirubin =< 2.0 mg/dL
6. Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional upper limit of normal
7. Creatinine =< 2.0 mg/dl
8. 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
9. Ability to understand and the willingness to sign a written informed consent document
10. STEP 2: INCLUSION CRITERIA PRIOR TO RANDOMIZATION
11. 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
12. 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
13. Resolution of all chemotherapy related grade III-IV toxicity as per Common Toxicity Criteria (CTC) criteria 4.0
14. Absolute neutrophil count (ANC) >= 1,000/uL
15. Platelets >= 50,000/uL
16. Bilirubin =< 2.0 mg/dL
17. Creatinine =< 2.0 mg/dL
18. AST/ALT =< 3.0 x upper limit of normal (ULN)
19. 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
20. STEP 3: ELIGIBILITY CRITERIA PRIOR TO TREATMENT OR OBSERVATION
21. Resolution of all chemotherapy related grade III-IV toxicity as per CTC criteria 4.0
22. White blood cells (WBC) >= 2.0 X 10^3/uL
23. Platelet >= 50,000/uL
24. Bilirubin =< 2.0 mg/ dL
25. Creatinine =< 2.0 mg/ dL
26. AST/ALT =< 3.0 x ULN
27. At least 2 doses of fusion vaccine were produced (Arm A only)
28. INCLUSION CRITERIA FOR PATIENTS PREVIOUSLY ENROLLED ON PROTOCOL 18-232
29. STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: Patients must have AML in first or second remission
30. 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
31. STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: Patients must be >= 55 years old
32. STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: ECOG performance status =< 2
33. STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: Total bilirubin =< 2.0 mg/dL
34. STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: AST(SGOT)/ALT(SGPT) =< 3 x institutional upper limit of normal
35. STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: Creatinine =< 2.0 mg/dl
36. STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: ANC >= 1,000/uL
37. STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: Platelets >= 50,000/uL
38. 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
39. STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: Ability to understand and the willingness to sign a written informed consent document
40. 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
41. 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
42. STEP 1/2: ELIGIBILITY CRITERIA FOR ENROLLMENT AND RANDOMIZATION: Resolution of all chemotherapy related grade III-IV toxicity as per CTC criteria 4.0
43. 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
44. STEP 3: ELIGIBILITY CRITERIA PRIOR TO TREATMENT OR OBSERVATION: Resolution of all chemotherapy related grade III-IV toxicity as per CTC criteria 4.0
45. STEP 3: ELIGIBILITY CRITERIA PRIOR TO TREATMENT OR OBSERVATION: WBC >= 2.0 X 10^3/uL
46. STEP 3: ELIGIBILITY CRITERIA PRIOR TO TREATMENT OR OBSERVATION: Platelets >= 50,000/uL
47. STEP 3: ELIGIBILITY CRITERIA PRIOR TO TREATMENT OR OBSERVATION: Bilirubin =< 2.0 mg/dL
48. STEP 3: ELIGIBILITY CRITERIA PRIOR TO TREATMENT OR OBSERVATION: Creatinine =< 2.0 mg/dL
49. STEP 3: ELIGIBILITY CRITERIA PRIOR TO TREATMENT OR OBSERVATION: AST/ALT =< 3.0 x ULN
50. STEP 3: ELIGIBILITY CRITERIA PRIOR TO TREATMENT OR OBSERVATION: At least 2 doses of fusion vaccine were produced (Arm A only)