Status and phase
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About
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
Full 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.
Enrollment
Sex
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Inclusion and exclusion criteria
Inclusion Criteria
Subjects have a pathologically confirmed diagnosis of AML by World Health Organization classification.
Subjects have AML that is refractory to or relapsed after induction therapy (i.e., subjects relapsed after experiencing a CR with their prior therapy). To be defined as relapse, there must be >5% blasts in the bone marrow.
Subjects are age ≥18 years at the time of signing informed consent.
Subjects have not received chemotherapy, radiation, or major surgery within 2 weeks prior to first dose of study drug and/or have recovered from the toxic side effects of any previous therapy, unless treatment is indicated as a result of progressive disease, such as hydroxyurea.
Subjects have not received investigational therapy within 4 weeks of the first dose of study drug.
Subjects have an Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
Subjects have adequate laboratory results including the following:
Subjects 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.
Exclusion Criteria
Primary purpose
Allocation
Interventional model
Masking
20 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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