Clinical trial NCT06372717: A Study to Investigate APL-4098 Alone and/or in Combination With Azacitidine in R/R AML and High-Risk MDS
Official title: A Phase 1/2 Study to Assess the Safety and Antitumor Activity of APL-4098 Alone and/or in Combination With Azacitidine in Adults With Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome/AML (MDS/AML) or Myelodysplastic Syndrome With Excess Blasts (MDS-EB)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Acute Myeloid Leukemia Refractory
Myelodysplastic Syndrome Acute Myeloid Leukemia
Myelodysplastic Syndrome With Excess Blasts
Acute Myeloid Leukemia, in Relapse
Lead sponsor: Apollo Therapeutics Ltd
Sponsor class: INDUSTRY
First posted: 2024-04-18
Enrollment: 122
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Treatment Emergent Adverse Events [Safety] (Phase 1)
timeFrame: Through study completion, approximately one year
measure: Incidence of Dose Limiting Toxicities [Tolerability] (Phase 1)
timeFrame: Cycle 1 Day 1 to Cycle 2 Day 1 (a cycle is 28 days)
measure: Determine Recommended Phase 2 Dose (RP2D)/Recommended dose range (RDR) levels of APL-4098 alone and/or in combination with azacitidine (Phase 1)
timeFrame: Approximately one year
measure: Assess the Pharmacokinetics of APL-4098 alone and/or in combination with azacitidine (Phase 1)
timeFrame: On Days 1, 2, 4, 8, and 15 of Cycle 1, and on Day 1 of Cycle 2 (each cycle is 28 days)
measure: Assess the Pharmacokinetics of APL-4098 alone and/or in combination with azacitidine (Phase 1)
timeFrame: On Days 1, 2, 4, 8, and 15 of Cycle 1, and on Day 1 of Cycle 2 (each cycle is 28 days)
measure: Assess the Pharmacokinetics of APL-4098 alone and/or in combination with azacitidine (Phase 1)
timeFrame: On Days 1, 2, 4, 8, and 15 of Cycle 1, and on Day 1 of Cycle 2 (each cycle is 28 days)
measure: Assess efficacy of APL-4098 alone and/or in combination with azacitidine (Phase 2)
timeFrame: 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)
Secondary outcomes:
measure: Assess response to disease with APL-4098 alone and/or in combination with azacitidine (Phase 1)
timeFrame: 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)
measure: Duration of response with APL-4098 alone and/or in combination with azacitidine [Further efficacy] (Phase 2)
timeFrame: From Cycle 1 Day 1 (a cycle is 28 days long) through end of study (approximately 2 years)
measure: Time to response with APL-4098 alone and/or in combination with azacitidine [Further efficacy] (Phase 2)
timeFrame: From Cycle 1 Day 1 (a cycle is 28 days long) through end of study (approximately 2 years)
measure: Event Free Survival with APL-4098 alone and/or in combination with azacitidine [Further efficacy] (Phase 2)
timeFrame: From Cycle 1 Day 1 (a cycle is 28 days long) through end of study (approximately 2 years)
measure: Overall Survival with APL-4098 alone and/or in combination with azacitidine [Further efficacy] (Phase 2)
timeFrame: From Cycle 1 Day 1 (a cycle is 28 days long) through end of study (approximately 2 years)
measure: Incidence of Treatment Emergent Adverse Events [Further Safety] (Phase 2)
timeFrame: Through study completion (approximately 2 years)
measure: Incidence of Adverse Events leading to discontinuation of APL-4098 [Further Tolerability] (Phase 2)
timeFrame: Through study completion (approximately 2 years)
measure: Further assess the PK of APL-4098 alone and/or in combination with azacitidine (Phase 2)
timeFrame: At Cycle 1 Day 1 and at Cycle 2 Day 1 (each cycle is 28 days)
measure: Further assess the PK of APL-4098 alone and/or in combination with azacitidine (Phase 2)
timeFrame: At Cycle 1 Day 1 and at Cycle 2 Day 1 (each cycle is 28 days)
measure: Further assess the PK of APL-4098 alone and/or in combination with azacitidine (Phase 2)
timeFrame: At Cycle 1 Day 1 and at Cycle 2 Day 1 (each cycle is 28 days)
Other outcomes:
Locations:
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Fitzroy
country: Australia
facility: St. Vincent's Hospital Melbourne
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Hollywood Private Hospital
state: Western Australia
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute UK
Study officials:
affiliation: Apollo Therapeutics
name: Sanjay Aggarwal, MD
role: STUDY_CHAIR
References: