CPX-351 and Ivosidenib for the Treatment of IDH1 Mutated Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

Inclusion Criteria:

Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
IDH1-R132 mutated disease status as assessed by local laboratory. 2HG-producing IDH1 variants outside of R132 (i.e. R100) may be eligible after discussion with the principal investigator (PI)
Treatment naive or relapsed/refractory AML who are eligible for intensive chemotherapy. Patients with high-risk MDS or MPN (defined as >= 10% bone marrow blasts, or intermediate or high risk by International Prognostic Scoring System [IPSS], revised [R]-IPSS or dynamic [D]-IPSS) may also be eligible after discussion with the PI
Direct bilirubin =< 2 x upper limit of normal (ULN) unless deemed to be related to underlying leukemia
Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) =< 3 x ULN unless deemed to be related to underlying leukemia
Creatinine clearance >= 30 ml/min based on the Cockcroft-Gault equation
Willing and able to provide informed consent
In the absence of rapidly proliferative disease, the interval from prior treatment to time of initiation will be at least 7 days for cytotoxic or non-cytotoxic (immunotherapy) agents
Male subjects must agree to refrain from unprotected sex and sperm donation from initial study drug administration until 90 days after the last dose of study drug

Exclusion Criteria:

Patients who have previously received either ivosidenib or CPX-351
Patients with any concurrent uncontrolled clinically significant medical condition including infection, laboratory abnormality, or psychiatric illness, which could place the patient at unacceptable risk of study treatment
The use of other chemotherapeutic agents or anti-leukemic agents is not permitted during study with the following exceptions (1) intrathecal chemotherapy for prophylactic use or for controlled central nervous system (CNS) leukemia. (2) use of hydroxyurea, and/or cytarabine (1 or 2 doses; up to 2 g/m^2) for patients with rapidly proliferative disease is allowed before the start of study therapy
Patients with active graft-versus-host-disease (GVHD) status post stem cell transplant (patients without active GVHD on chronic suppressive immunosuppression and/or phototherapy for chronic skin GVHD are permitted after discussion with the PI)
Patients with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications
Patients with symptomatic congestive heart failure (New York Heart Association [NYHA] class III or IV), unstable angina, or an ejection fraction < 45%
Patients with prior anthracycline exposure of > 360 mg/m^2 daunorubicin (or equivalent) or > 210 mg/m^2 daunorubicin (or equivalent) in patients with prior mediastinal radiation
Corrected QT (QTc) interval using Fridericia's formula (QTcF) >= 470 msec. A prolonged QTc interval in the setting of right bundle branch block is permitted after discussion with the PI

Nursing women, women of childbearing potential (WOCBP) with positive urine or serum pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception

Appropriate highly effective method(s) of contraception include oral or injectable hormonal birth control, intrauterine device (IUD), and double barrier methods (for example a condom in combination with a spermicide)
Subjects with a known medical history of progressive multifocal leukoencephalopathy (PML)
Subjects taking strong CYP3A4 inducers are excluded from the study unless they can be transferred to other medications within >= 5 half lives prior to dosing
Patients with a diagnosis of acute promyelocytic leukemia (APL)
Unresolved toxicities > grade 1 from prior treatment including chemotherapy, targeted therapy, immunotherapy, experimental agents, radiation, or surgery