Lower Doses of CPX-351 for the Treatment of Older Patients with Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome

Inclusion Criteria

• Primary refractory or relapsed acute myeloid leukemia (AML) (defined by 2016 World Health Organization [WHO] criteria) patients who are not suitable for or not willing to receive intensive chemotherapy as evaluated by the treating physician. Primary refractory disease is defined as: * Failure to achieve a CR, complete response with incomplete hematologic recovery (CRi), or morphologic leukemia-free state (MLFS) (defined as < 5% bone marrow [BM] blasts) after receiving 4 cycles of non-intensive chemotherapy or whose disease progressed at any time point during the treatment
• Patients with myelodysplastic syndrome (MDS) (according to 2016 WHO criteria) who did not respond to treatment with azacitidine, decitabine, or combination of hypomethylating agents (HMA) with another drug or lost their response to initial therapy with HMA. Primary resistance to therapy is defined according to Cheson et al 2006: * Primary resistance occurs when, while receiving therapy without experiencing hematologic improvement (HI) at any time, the patient progresses to overt acute myeloid leukemia (> 20% BM blasts); the patient progresses to higher-risk MDS; even after 4 to 6 cycles, the patient has stable disease without any of the following: HI, complete remission (CR), marrow CR (mCR), or partial remission (PR), according to International Working Group criteria; or the patient develops hypoplastic marrow and pancytopenia. * Secondary resistance occurs when, after initial response (CR, mCR, PR, HI) has been maintained for any number of cycles and without therapy interruption or delays exceeding 5 weeks between cycles, the treated patient has any of the primary resistance conditions
• Age >= 60 years
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Serum total bilirubin =< 1.5 x upper limit of normal (ULN) (up to 3 mg/dL will be eligible for this trial)
• Serum glutamic pyruvic transaminase (SGPT) and/or serum glutamic oxaloacetic transaminase (SGOT) =< 2.5 x ULN
• Creatinine clearance >= 30mL/min
• Patients must be willing and able to review, understand, and provide written consent before starting therapy

Exclusion Criteria

• Active signs or symptoms of central nervous system (CNS) involvement by malignancy (lumbar puncture [LP] not required)
• Prior 7+3 remission induction chemotherapy for MDS or AML *Please note* Prior anthracycline exposure plus anticipated maximum exposure on this trial should not exceed a lifetime daunorubicin equivalent of 550 mg/m^2 or 400 mg/m^2 in patients who received radiation therapy to the mediastinum
• New York Heart Association (NYHA) class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia on rhythm control strategy or on pacemaker, uncontrolled hypertension (blood pressure > 160 systolic and > 110 diastolic not responsive to antihypertensive medication)
• Acute myocardial infarction in the previous 12 weeks (from the start of treatment)
• Any serious medical condition, laboratory abnormality, or psychiatric illness that, in the view of the treating physician, would place the participant at an unacceptable risk if he or she were to participate in the study or would prevent that person from giving informed consent
• Any active malignancy (unrelated, non-hematological malignancy) diagnosed within the past 6 months of starting the study drug (other than curatively treated carcinoma-in-situ of the cervix or non-melanoma skin cancer)
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to CPX-351
• Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Uncontrolled or untreated human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
• No major surgery within 2 weeks prior to study enrollment
• Pregnant or breast feeding
• Male and female patients who are fertile who do not agree to use an effective barrier methods of birth control (i.e. abstinence) to avoid pregnancy while receiving study treatment and for 30 days after last dose of study treatment. Non-childbearing is defined as > 1 year postmenopausal or surgically sterilized
• Acute promyelocytic leukemia (APL)