Phase 1/2 Study of Liposomal Annamycin for the Treatment of Subjects With Acute Myeloid Leukemia (AML) That is Refractory to or Relapsed After Induction Therapy

Enrollment will occur in cohorts of 3 subjects in a conventional 3+3 escalating dose design, starting at a dose level of 120 mg/m2/day administered for 3 days. Dose escalation will take place on the basis of safety assessments in sequential cohorts of 3 subjects each. The initial cohort will receive 120 mg/m2/day for 3 days. For Cohorts 1, 2, 3, 4, and 5, dose escalation will occur in 30-mg/m2/day increments until subjects are enrolled at a 240-mg/m2/day dose. For Cohorts 6, 7, and 8, dose escalation will occur in 60-mg/m2/day increments until subjects are enrolled at a maximum dose of 420 mg/m2/day. Thus subsequent cohorts will receive 150, 180, 210, 240, 300, 360, and up to a maximum of 420 mg/m2/day for 3 days in the absence of safety concerns.

In each cohort during the dose escalation phase, if 1 of the 3 subjects experiences a DLT, the cohort of subjects at that dose level 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 next 3 subjects will be treated at a lower dose. The dose will be de-escalated in 30-mg/m2/day increments. As such, if at least 2 out of 6 subjects receiving 300, 360, or 420 mg/m2/day experience a DLT, the next 3 subjects will receive 270, 330, or 390 mg/m2/day, respectively. The MTD is defined as the highest dose of L-Annamycin at which fewer than 2 (of a cohort of up to 6) subjects experience a DLT.

Once the MTD/RP2D is identified, up to 21 additional subjects will be enrolled at the MTD/RP2D to better define toxicity and evaluate efficacy at this dose.