Study of Liposomal Annamycin for the Treatment of Subjects With Acute Myeloid Leukemia (AML)
- Registration Number
- NCT03388749
- Lead Sponsor
- Moleculin Biotech, Inc.
- Brief Summary
This is a multi-center, open-label, dose escalation study that will determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of liposomal annamycin as a single agent for the treatment of subjects with AML that is refractory to or relapsed after induction therapy
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 20
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Liposomal annamycin Liposomal Annamycin -
- Primary Outcome Measures
Name Time Method Evaluation of safety and identification of the MTD/RP2D for L-Annamycin Day 1 through Day 28 The number of patients who experience dose-limiting toxicities (DLT) will be captured at each dose level of L-Annamycin in order to determine the MTD/RP2D
- Secondary Outcome Measures
Name Time Method Anti-leukemic activity Between Day 15 and Day 35 (+/- 3 days) Determined by acute myeloid leukemia (AML) response rate based on the International Working Group (IWG) Response Criteria in AML (Cheson, 2003). Leukemia response rate will be evaluated by the investigator at the end of each L-Annamycin cycle based on bone marrow aspirate and peripheral blood evaluations.
Pharmacokinetics - Area under the plasma concentration Day 1 and Day 3 Area under the plasma concentration - time curve (AUC) of annamycin and its metabolite, annamycinol
Trial Locations
- Locations (5)
Samodzielny Szpital Kliniczny nr 1
🇵🇱Wrocław, Poland
Szpital Kliniczny Przemienienia Pańskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego
🇵🇱Poznań, Poland
Samodzielny Publiczny Szpital Kliniczny nr 1 im. Prof. Tadeusza Sokołowskiego w Szczecinie, Klinika Hematologii z Oddziałem Transplantacji Szpiku
🇵🇱Szczecin, Poland
Medical University of Lodz
🇵🇱Łódź, Poland
Instytut Hematologii i Transfuzjologii, Klinika Hematologii
🇵🇱Warszawa, Poland