Phase I/II Clinical Trial of Proteasome Inhibitor in Combination With CPX-351 for the Treatment of Newly-Diagnosed TP53-mutated Acute Myeloid Leukemia (AML)

Inclusion Criteria: * Adult (age ≥ 18 years at time of consent) * Have not received any systemic chemotherapy for the treatment of AML. Use of hydroxyurea and leukapheresis to control excess peripheral blasts is permissible. WBC \< 25,000 to initiate bortezomib, must reach this threshold by day 7 of CPX-351. * Karnofsky performance status (KPS) ≥ 70 * Adequate renal, hepatic and cardiac function defined as * Renal: An estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2 * Hepatic: AST and ALT ≤3 x ULN, ALP ≤2.5 x ULN, and total bilirubin ≤1.5 x ULN. (exception for Gilbert's syndrome or leukemic infiltration of liver) * Cardiac: New York Heart Association (NYHA) Class I or II, left ventricular ejection fraction \> 50% by echocardiogram, MUGA or cardiac MRI * Sexually active couples of childbearing potential must agree to use effective contraception or abstinence during treatment and for at least 7 months after the final dose of study drug * Provides voluntary written consent before the performance of any study related activities not part of standard of care. Exclusion Criteria: * Received systemic chemotherapy for the treatment of AML * Bi-phenotypic acute leukemia or mixed lineage leukemia, acute promyelocytic leukemia * Active central nervous system malignancy or symptoms of CNS involvement * Symptomatic extramedullary disease * Known history of uncontrolled HIV or active hepatitis B or active hepatitis C infection * Has any of the following cardiac abnormalities * Symptomatic congestive heart failure * Myocardial infarction less than or equal to 6 months prior to enrollment * Unstable angina pectoris * Serious uncontrolled cardiac arrhythmia * Concomitant malignancies or previous malignancies with less than a 1-year disease free interval at the time of signing consent. Potential participants with adequately resected basal or squamous cell carcinoma of the skin, or adequately resected carcinoma in situ (e.g., cervix) may enroll irrespective of the time of diagnosis * Participants for whom administration of CPX-351 would exceed their lifetime cumulative daunorubicin exposure limit of 550 mg/m2 (or 400 mg/m2 in patients with prior chest radiation) or equivalent anthracycline dose. * Pregnant or breastfeeding, or planning pregnancy within 3 months after the treatment completion