A Phase Ib/II Study of APG-115 Alone or in Combination With Azacitidine in Patients With Relapse/Refractory AML, CMML or MDS
This is a two Part study in patients with relapsed/refractory acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), or high risk myelodysplastic syndrome (MDS) that will initially evaluate the safety and tolerability of APG-115 as a single agent in Part 1, followed by a combination of APG-115 + 5-azacitidine (5-AZA) in Part 2.
• Patients with a diagnosis of histologically confirmed relapsed or refractory AML, CMML, or high-risk MDS (overall revised international prognostic scoring system (IPSS-R) score \> 3, including intermediate, high, or very high risk) by World Health Organization (WHO) classification for which no available standard therapies are indicated or anticipated to result in a durable response.
• Adequate organ function as defined below:
‣ Liver function (total bilirubin \< or = 1.5 x upper limit of normal (ULN), aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \<3 x ULN
⁃ Kidney function (defined as a calculated creatinine clearance ≥ 60 mL/min; determined via urine collection for 24-hour creatinine clearance or by the Cockcroft Gault formula)
⁃ Known cardiac ejection fraction of \> or = 45% within the past 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• A negative serum pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.
• Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient or legally authorized representative is required prior to their enrollment on the protocol.
• Subject must have a projected life expectancy of at least 12 weeks.
• Subject has a white blood cell count \< 25 × 10˄9/L. Note: Hydroxyurea is permitted to meet this criteria.