Overview
This is an open-label, Phase 1/2 study to determine the safety, tolerability, and efficacy of APL-4098 alone and/or in combination with azacitidine for the treatment of relapsed or refractory (R/R) acute myeloid leukemia (AML), myelodysplastic syndrome (MDS)/AML and MDS-excess blasts (EB). Participants with the MDS-EB subtype will be eligible for the Phase 1 part of the study only.
Eligibility
Inclusion Criteria:
- 18 years or older
- Confirmed diagnosis of relapsed refractory acute myeloid leukemia (R/R AML), myelodysplastic syndrome (MDS)/ AML, or MDS-excess blasts (MDS-EB) with the following characteristics: - R/R AML (primary or secondary, including treatment-related), participant is intolerant to, or considered ineligible for available therapies known to provide clinical benefit.
- WBC count ≤ 25,000/microliter
- ECOG Performance Status of ≤ 2
- Weight ≥ 40kg
- Female participants of childbearing potential must have negative serum pregnancy test at screening; must not plan to become pregnant or have ova harvested or breastfeed while on study; must we willing to use specific contraception or avoid intercourse
- Male participants must be willing to use specific contraception and not plan to impregnant a female partner or donate sperm while on study
- Participant must be willing and able to provide written informed consent and to comply with the requirements of the trial
Exclusion Criteria:
- Certain prior therapies such as: received an allogeneic stem cell transplant within 6 months of screening, received an autologous stem cell transplant within 3 months of screening, received any anti-cancer treatments within 2 weeks of Cycle 1 Day 1, prior radiation therapy within 4 weeks of screening
- Certain medical conditions such as: other malignancies, myocardial infarction within 6 months of screening, symptomatic congestive heart failure, uncontrolled active infection, history of arterial thrombosis within 6 months of screening
- Diagnostic assessments: Left ventricular ejection fraction < 45%, Fridericia's corrected QT interval > 470msec, Aspartate aminotransferase and/or alanine aminotransferase > 3 x upper limit of normal (ULN), total bilirubin > 1.5 x ULN, calculated or measured creatinine clearance < 45 mL/minute (multiply by 0.85 if female)
- Infectious disease: HIV positive, active hepatitis B and/or C