Acute Myeloid Leukemia (AML), Acute Myeloid Leukemia, in Relapse, Acute Myeloid Leukemia Refractory, Myelodysplastic Syndrome Acute Myeloid Leukemia, Myelodysplastic Syndrome With Excess Blasts
Conditions
Brief 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).
Interventions
DRUGAPL-4098
APL-4098 is administered orally in 28-day cycles
DRUGAzacitidine 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.
DRUGAzacitidine 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.
Sponsors
Apollo Therapeutics Ltd
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assess response to disease with APL-4098 alone, in combination with azacitidine, and in combination with azacitidine plus venetoclax. | Response is assessed at Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 7 Day 1 (each cycle is 28 days long), then every three cycles thereafter (assessed for up to 2 years) | R/R AML and MDS/AML participants: response is assessed per European LeukemiaNet (ELN) 2022 criteria MDS-EB participants: response is assessed per revised International Working Group 2023 response criteria |
Countries
Australia, United Kingdom
Contacts
CONTACTApollo Therapeutics
STUDY_CHAIRSanjay Aggarwal, MD
Apollo Therapeutics
Outcome results
None listed