CPX-351 Plus Enasidenib for Relapsed AML

Inclusion Criteria:

* Bone marrow blasts \>= 5% that develops after CR/CRi in patient with prior history of AML, no restriction on prior number of relapses or regimens
* AML characterized by the IDH2 gene mutation, without requirement for a particular allelic frequency
* Patients previously treated with IDH2 inhibitor can be enrolled
* At least a 3-month duration of CR/CRi prior to relapse
* Relapses after allogeneic HSCT are included with a minimum of 3 from the date of allogeneic HSCT
* Up to 1 cycle of hypomethylating agent monotherapy at time of relapse is allowed, must be discontinued at least 14 days prior to start of salvage induction
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Serum total bilirubin \< 2.0 mg/dL, unless considered due to Gilbert's disease or leukemic involvement
* Aspartate aminotransferase (AST), alanine aminotransferase (ALT) \< 3 times the upper limit of normal, unless considered due to leukemic involvement
* Alkaline phosphatase \< 3 times the upper limit of normal, unless considered due to leukemic involvement
* Serum creatinine =\< 2.0 mg/dL, or creatinine clearance \> 40 mL/min based on Cockcroft-Gault glomerular filtration rate (GFR)
* Females of reproductive potential as well as fertile men and their partners who are female of reproductive potential must agree to abstain from sexual intercourse or to use two highly effective forms of contraception from the time of giving informed consent, during the study, and for four months (females and males) following the last dose of IDH inhibitor. A highly effective form of contraception is defined as hormonal oral contraceptives, injectables, patches, intrauterine devices, double-barrier method (eg, synthetic condoms, diaphragm or cervical cap with spermicidal foam, cream, or gel) or male partner sterilization

Exclusion Criteria:

* Concurrent FLT3 mutation that the treating physician deems necessary to treat with FLT3-targeted therapy; whereas, patients with FLT3-mutated AML not treated with FLT3-targeted therapy can be enrolled
* Acute promyelocytic leukemia
* Inability to swallow medications or history of gastrointestinal (GI) malabsorptive disease
* Active malignancy that would limit survival by less than two years
* New York Heart Association class III or VI
* Left ventricular ejection fraction \< 40%
* History of coronary stent placement that require mandatory continuation of dual-antiplatelet therapy
* Baseline QT corrected interval based on Fridericia's formula (QTcF) interval \> 450 ms
* History of Wilson's disease or other copper handling disorders
* Hypersensitivity to cytarabine, daunorubicin, or liposomal products
* Active invasive fungal infection
* Active bacterial or viral infection manifesting as fevers or hemodynamic instability within the past 72 hours
* Lifetime cumulative daunorubicin-equivalent anthracycline dose \> 368 mg/m\^2
* Pregnant or breast feeding