Acute Myeloid Leukemia RefractoryMyelodysplastic Syndrome Acute Myeloid LeukemiaMyelodysplastic Syndrome With Excess BlastsAcute Myeloid Leukemia, in RelapseAcute Myeloid Leukemia (AML)
Investigational drug(s) / intervention(s)
APL-4098Azacitidine and APL-4098Azacitidine and Venetoclax and APL-4098
APL-4098: APL-4098 is administered orally in 28-day cycles
Azacitidine and APL-4098: Azacitidine is administered at the standard dose on Day 1 - Day 7 of each 28-day cycle; APL-4098 is administered orally.
Azacitidine and Venetoclax and APL-4098: Azacitidine is administered at the standard dose on Day 1 - Day 7 of each 28-day cycle; Venetoclax is administered orally; APL-4098 is administered orally.
Study summary
This is an open-label, Phase 1 study to determine the safety, tolerability, and efficacy of APL-4098 alone, and in combination with azacitidine, and in combination with azacitidine plus venetoclax for the treatment of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS)/AML and MDS-excess blasts (EB).
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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 be 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
Primary outcome measure(s)
Incidence of Treatment Emergent Adverse Events [Safety] — Through study completion, approximately one year Evaluation of safety parameters including treatment emergent adverse events as detected by hematology, chemistry, coagulation safety labs, physical exams, vital signs, Electrocardiogram results
Incidence of Dose Limiting Toxicities [Tolerability] — Cycle 1 Day 1 to Cycle 2 Day 1 (a cycle is 28 days) Evaluation of tolerability parameters including dose limiting toxicities as detected by hematology, chemistry, coagulation safety labs, physical exams, vital signs, and Electrocardiogram results
Determine Recommended Phase 2 Dose (RP2D)/Recommended dose range (RDR) levels of APL-4098 alone, in combination with azacitidine, and in combination with azacitidine plus venetoclax. — Approximately one year
Assess the Pharmacokinetics of APL-4098 — On Days 1, 2, 8, and 15 of Cycle 1, and on Day 1 of Cycle 2 (each cycle is 28 days) Evaluate PK parameters: Maximum plasma concentration (Cmax)
Assess the Pharmacokinetics of APL-4098 — On Days 1, 2, 8, and 15 of Cycle 1, and on Day 1 of Cycle 2 (each cycle is 28 days) Evaluate PK parameters: area under the curve (AUC)
Assess the Pharmacokinetics of APL-4098 — On Days 1, 2, 8, and 15 of Cycle 1, and on Day 1 of Cycle 2 (each cycle is 28 days) Evaluate PK parameters: Time to peak concentration (Tmax)
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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