IMetelstat and Azacitidine With or Without Venetoclax GIveN in rElapsed Acute Myeloid Leukemia (IMAGINE Trial)
Douglas Tremblay
Summary
IMAGINE is a two-part trial to evaluate the safety and preliminary efficacy of imetelstat in combination with azacitidine with or without venetoclax in patients with relapsed or refractory AML. The trial will consist of a safety run-in phase (Part A) employing a 3+3 design to monitor dose-limiting toxicities of imetelstat when administered in combination with a fixed dose of azacitidine. Part B will consist of a phase 1b trial employing a BOIN12 design to determine the optimal biological dose of imetelstat, starting at a lower dose level, in combination with azacitidine and venetoclax. Total of up to 36 participants will be accrued over 54 months at Mount Sinai Hospital. Estimated duration of trial is 114 months including recruitment, screening, treatment, and follow-up.
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria In order to be eligible for participation in this trial, * Participants must be ≥18 years of age at time of signing the Informed Consent Form (ICF). * Participants must voluntarily sign an ICF. * Participants must have WHO-confirmed non-APL AML who have not responded to or relapsed after at least one prior therapy and for whom no standard therapy that may provide clinical benefit is available. o Participants with isolated extramedullary disease (EMD), including leukemia cutis, are included but not those with active known CNS disease. * Participants must have a life expec…
Interventions
- DrugImetelstat
Three 3 dose levels administered on Day 1 of each 28-day cycle for Safety Run-in Phase and optimal dose to be administered on Day 1 of each 28-day cycle
- DrugAzacitidine
75mg/m2 IV or subcutaneous (SQ) once daily for Days 1 (+/- 1 day) through 7 (+/- 1 day) of each 28-day cycle. Azacitidine can be administered locally as long as documentation of administration is provided to the study team.
- DrugVenetoclax
Venetoclax 400mg oral once daily for Days 1 (+/- 1 day) through 14 (+/- 1 day) of each 28-day cycle. Venetoclax reduced dosey should be substituted if concomitant posaconazole, or if other concomitant strong CYP3A4 inhibitor (e.g. voriconazole) or 200mg for moderate CYP3A4 inhibitor (e.g. isavuconazole). For Cycle 1, participants will receive a venetoclax ramp-up dose on day 1, day 2, and days 3-14 of venetoclax,. If the participant is being treated with concomitant posaconazole, or other concomitant strong CYP3A4 inhibitor, or with a concomitant moderate CYP3A4 inhibitor or a pg-p inhibitor, participants will receive a lower ramp-up dose on day 1, day 2, and days 3-14 of venetoclax.
Location
- Icahn School of Medicine at Mount SinaiNew York, New York