A Study to Investigate APL-4098 Alone and/or in Combination With Azacitidine in R/R AML and High-Risk MDS
- Conditions
- Acute Myeloid Leukemia, in RelapseAcute Myeloid Leukemia RefractoryMyelodysplastic Syndrome Acute Myeloid LeukemiaMyelodysplastic Syndrome With Excess Blasts
- Interventions
- Registration Number
- NCT06372717
- Lead Sponsor
- Apollo Therapeutics Ltd
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 122
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation Phase: APL-4098 monotherapy APL-4098 Dose escalation with different dosing levels of APL-4098. Phase 2 Dose Expansion: APL-4098 and azacitidine Azacitidine and APL-4098 - Dose Escalation Phase: APL-4098 and azacitidine Azacitidine and APL-4098 Dose escalation with different dosing levels of APL-4098 in combination with azacitidine (75 mg/m2). Phase 2 Dose Expansion: APL-4098 monotherapy APL-4098 -
- Primary Outcome Measures
Name Time Method Assess the Pharmacokinetics of APL-4098 alone and/or in combination with azacitidine (Phase 1) On Days 1, 2, 4, 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)
Assess efficacy of APL-4098 alone and/or in combination with azacitidine (Phase 2) 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) Response is assessed per European LeukemiaNet 2022 criteria
Incidence of Treatment Emergent Adverse Events [Safety] (Phase 1) 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] (Phase 1) 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 and/or in combination with azacitidine (Phase 1) Approximately one year
- Secondary Outcome Measures
Name Time Method Event Free Survival with APL-4098 alone and/or in combination with azacitidine [Further efficacy] (Phase 2) From Cycle 1 Day 1 (a cycle is 28 days long) through end of study (approximately 2 years) Time to response with APL-4098 alone and/or in combination with azacitidine [Further efficacy] (Phase 2) From Cycle 1 Day 1 (a cycle is 28 days long) through end of study (approximately 2 years) Assess response to disease with APL-4098 alone and/or in combination with azacitidine (Phase 1) 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
Further assess the PK of APL-4098 alone and/or in combination with azacitidine (Phase 2) At Cycle 1 Day 1 and at Cycle 2 Day 1 (each cycle is 28 days) Evaluate PK parameters: Time to peak concentration (Tmax)
Duration of response with APL-4098 alone and/or in combination with azacitidine [Further efficacy] (Phase 2) From Cycle 1 Day 1 (a cycle is 28 days long) through end of study (approximately 2 years) Overall Survival with APL-4098 alone and/or in combination with azacitidine [Further efficacy] (Phase 2) From Cycle 1 Day 1 (a cycle is 28 days long) through end of study (approximately 2 years) Incidence of Treatment Emergent Adverse Events [Further Safety] (Phase 2) Through study completion (approximately 2 years) 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 Adverse Events leading to discontinuation of APL-4098 [Further Tolerability] (Phase 2) Through study completion (approximately 2 years)
Trial Locations
- Locations (6)
Royal Perth Hospital
🇦🇺Perth, Western Australia, Australia
Sarah Cannon Research Institute UK
🇬🇧London, United Kingdom
Monash Health
🇦🇺Clayton, Victoria, Australia
St. Vincent's Hospital Melbourne
🇦🇺Fitzroy, Victoria, Australia
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Hollywood Private Hospital
🇦🇺Nedlands, Western Australia, Australia