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

During Phase 1b, dose escalation will proceed according to a standard 3+3 design. An initial group of 3 subjects will be treated with an intravenous infusion of 190-mg/m2 L-Annamycin (Dose Level 1) for 3 consecutive days. Dose escalation will take place on the basis of safety assessments in sequential cohorts of 3 subjects each. Provided that there are no DLT's in the initial cohort of subjects treated at the 190 mg/m2/day dose level, the next cohort of subjects will receive the next highest L-Annamycin dose incremented by 40 mg/m2. In the absence of DLTs, dose escalation by 40 mg/m2 will continue in subsequent cohorts until an MTD is reached.

The dose and schedule of cytarabine during Cycle 1 (2.0 g/m2/day for 5 consecutive days) will remain constant for all cohorts. Enrolled subjects will receive cytarabine at a dose of 2.0 g/m2/day via intravenous infusion over 4 hours for 5 consecutive days (total dose cytarabine = 10.0 g/m2; starting on the first day of L-Annamycin treatment).

If no subject experiences a dose-limiting toxicity (DLT), based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5, which constitutes a study drug-related irreversible or not medically manageable Grade 3 or higher toxicity during the initial treatment through Day 28, the subsequent group of 3 subjects will receive the next higher L-Annamycin dose. However, if 1 of the 3 initial subjects experiences a DLT, the cohort of subjects at that dose level will be expanded to 6. If at least 2 of the 6 subjects experience a DLT, this will be considered a non-tolerated dose and the next 3 subjects will be treated at a lower dose. The dose of L-Annamycin will be de-escalated by 20- mg/m2/day. As such, if at least 2 out of 6 subjects receiving 230 mg/m2/day experience a DLT, the next 3 subjects will receive L-Annamycin at a dose of 210 mg/m2/day. If 1 of the 3 initial subjects experiences a DLT, the cohort of subjects will be expanded to 6 subjects. If at least 2 of the 6 subjects experience a DLT, this will be considered a toxic dose and the MTD will be the previously proven safe dose level (i.e., the next lowest dose level at which no DLTs occurred in a cohort of 3 subjects or at which fewer than 2 subjects in a cohort of 6 experienced a DLT).

In the expansion phase, up to 21 subjects will be enrolled at the MTD/RP2D to better define toxicity and evaluate efficacy.