IMetelstat and Azacitidine With or Without Venetoclax GIveN in rElapsed Acute Myeloid Leukemia (IMAGINE Trial)
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.
• 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 expectancy of at least 12 weeks per investigator.
• ECOG performance status ≤ 3.
• Women of child bearing potential (WOCBP), defined as a sexually mature woman not surgically sterilized or post-menopausal for at least 24 consecutive months if ≤55 years or 12 months if \>55 years, must have a negative serum pregnancy test at screening and cycle 1 day 1 and must agree to use highly effective methods of birth control starting with the first dose of study therapy through 6 months after the last dose of study therapy. Highly effective methods of contraception include double-barrier methods (diaphragm with spermicidal gel and condoms with spermicide), partner vasectomy, and total abstinence
• Male participants should agree to use a highly effective method of contraception starting with the first dose of study therapy through 6 months after the last dose of study therapy. 8. Must have adequate organ function as demonstrated by the following:
‣ Serum total bilirubin ≤ 2.0 x upper limit of normal (ULN) unless considered due to leukemic organ involvement or Gilbert's syndrome.
⁃ Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN.
⁃ Creatinine clearance (CrCl) ≥ 30 mL/min (measured or estimated by Cockcroft-Gault formula).
• Ability to adhere to the study visit schedule and all protocol requirements.
• Ability to understand and the willingness to sign a written informed consent.