Study of Liposomal Annamycin for the Treatment of Subjects With Acute Myeloid Leukemia (AML)

Inclusion criteria

• A pathologically confirmed diagnosis of AML by World Health Organization (WHO) classification.
• AML that is refractory to or relapsed after standard induction therapy.
• Age ≥18 years at the time of signing informed consent.
• No chemotherapy, radiation, or major surgery within two weeks prior to first dose of study drug and/or recovered from the toxic side effects of that therapy, unless treatment is indicated due to progressive disease.
• No investigational therapy within four weeks of the first dose of study drug.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
• Adequate laboratory results including the following:

• Bilirubin ≤1.5 times the upper limit of normal (ULN) unless due to Gilbert Syndrome
• Serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT) and alkaline phosphatase <3 times the ULN) unless due to organ involvement
• Adequate renal function (The Cockcroft-Gault equation will be used to estimate creatinine clearance. This equation is as follows: Creatinine clearance in ml/min = (140 - age) x body weight (kg)/72 x plasma creatinine (mg/dL); multiplied by 0.85 for women. Using this equation, adequate renal function will be deemed to be a creatinine clearance of greater than 60 ml/minute.)
• Prior anthracycline cumulative dose below 551 mg/m2 or the daunorubicin equivalent which is the recommended non-cardiotoxic level.
• Subject can understand and sign the informed consent document, can communicate with the investigator, and can understand and comply with the requirements of the protocol.
• Women of childbearing potential must have a negative serum or urine pregnancy test.
• All men and women must agree to practice effective contraception during the entire study period and after discontinuing study drug, unless documentation of infertility exists.

• Sexually active, fertile women must use two effective forms of contraception (abstinence, intrauterine device, oral contraceptive, or double barrier device) from the time of informed consent and until at least 6 months after discontinuing study drug
• Sexually active men and their sexual partners must use effective contraceptive methods from the time of subject informed consent and until at least 3 months after discontinuing study drug

Exclusion criteria

• Subjects diagnosed with Acute Promyelocytic Leukemia.
• Concomitant therapy that includes other chemotherapy that is or may be active against AML except for prophylaxis and/or treatment of opportunistic or other infection with antibiotics, antifungals and/or antiviral agents.
• Prior mediastinal radiotherapy
• Any condition which, in the opinion of the Investigator, places the subject at unacceptable risk if he/she were to participate in the study.
• Positive risk assessment for cardiovascular disease including prior anthracycline cumulative dose more than 50% above recommended non-cardiotoxic levels, left ventricular ejection fraction (LVEF) <50%, valvular heart disease, or severe hypertension, (see Table 1). Cardiac subjects with a New York Heart Association (NYHA) classification of 3 or 4 will be excluded. (Cardiology consultation should be requested if any question arises about cardiac function.) This also includes subjects with baseline QT/QTc interval >480 msec, a history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) and using concomitant medications that significantly prolong the QT/QTc interval.
• Clinically relevant serious co-morbid medical conditions including, but not limited to, active infection, recent (less than or equal to six months) myocardial infarction, unstable angina, symptomatic congestive heart failure, uncontrolled hypertension, uncontrolled cardiac arrhythmias, chronic obstructive or chronic restrictive pulmonary disease, active CNS disease uncontrolled by standard of care, known positive status for human immunodeficiency virus (HIV) and/or active hepatitis B or C, cirrhosis, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant, lactating, or not using adequate contraception.
• Known allergy to anthracyclines.
• Any evidence of mucositis/stomatitis or previous history of severe (≥Grade 3) mucositis from prior therapy.
• Required use of strong inhibitors and inducers of CYP enzymes and transporters.