NCT05319587

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

Phase 1/2 Study of Liposomal Annamycin in Combination With Cytarabine for the Treatment of Subjects With Acute Myeloid Leukemia (AML)

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 22 (actual)
• Sponsor: Moleculin Biotech, Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a Phase 1/2, multicenter, open-label, dose-escalation study that will determine the MTD and RP2D of L-Annamycin in combination with cytarabine for the treatment of subjects with AML.

Detailed description

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.

Conditions

• Leukemia, Myeloid, Acute

Interventions

Type	Name	Description
DRUG	Liposomal Annamycin	2-hour intravenous infusion liposomal annamycin daily for 3 consecutive days followed by 18 days off study drug (i.e., one treatment cycle = 21 days).
DRUG	Cytarabine	Administered during cycle 1 at a dose of 2.0 g/m2/day by 4 hours IV infusion for 5 consecutive days and this dose will remain constant for all cohorts, including the expansion phase.

Timeline

• Start date: 2022-09-29
• Primary completion: 2023-08-02
• Completion: 2023-08-10
• First posted: 2022-04-08
• Last updated: 2025-09-30

Locations

9 sites across 2 countries: Italy, Poland

Regulatory

• FDA-regulated drug study