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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06372717




Registration number
NCT06372717
Ethics application status
Date submitted
11/03/2024
Date registered
18/04/2024
Date last updated
9/07/2024

Titles & IDs
Public title
A Study to Investigate APL-4098 Alone and/or in Combination With Azacitidine in R/R AML and High-Risk MDS
Scientific 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)
Secondary ID [1] 0 0
AP30CP01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia Refractory 0 0
Myelodysplastic Syndrome Acute Myeloid Leukemia 0 0
Myelodysplastic Syndrome With Excess Blasts 0 0
Acute Myeloid Leukemia, in Relapse 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Blood 0 0 0 0
Anaemia
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Blood 0 0 0 0
Haematological diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - APL-4098
Treatment: Drugs - Azacitidine and APL-4098

Experimental: Dose Escalation Phase: APL-4098 monotherapy - Dose escalation with different dosing levels of APL-4098.

Experimental: Dose Escalation Phase: APL-4098 and azacitidine - Dose escalation with different dosing levels of APL-4098 in combination with azacitidine (75 mg/m2).

Experimental: Phase 2 Dose Expansion: APL-4098 monotherapy -

Experimental: Phase 2 Dose Expansion: APL-4098 and azacitidine -


Treatment: Drugs: APL-4098
APL-4098 is administered orally in 28-day cycles

Treatment: Drugs: Azacitidine and APL-4098
Azacitidine is administered at the standard dose of 75mg/m2 on Day 1 - Day 7 of each 28-day cycle; APL-4098 is administered orally.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of Treatment Emergent Adverse Events [Safety] (Phase 1)
Timepoint [1] 0 0
Through study completion, approximately one year
Primary outcome [2] 0 0
Incidence of Dose Limiting Toxicities [Tolerability] (Phase 1)
Timepoint [2] 0 0
Cycle 1 Day 1 to Cycle 2 Day 1 (a cycle is 28 days)
Primary outcome [3] 0 0
Estimate the Maximum Tolerated Dose (MTD) of APL-4098 alone and/or in combination with azacitidine (Phase 1)
Timepoint [3] 0 0
Cycle 1 Day 1 to Cycle 2 Day 1 (a cycle is 28 days)
Primary outcome [4] 0 0
Determine Recommended Phase 2 Dose (RP2D) levels of APL-4098 alone and/or in combination with azacitidine (Phase 1)
Timepoint [4] 0 0
Approximately one year
Primary outcome [5] 0 0
Assess the Pharmacokinetics of APL-4098 alone and/or in combination with azacitidine (Phase 1)
Timepoint [5] 0 0
On Days 1, 2, 4, 8, and 15 of Cycle 1, and on Day 1 of Cycle 2 (each cycle is 28 days)
Primary outcome [6] 0 0
Assess the Pharmacokinetics of APL-4098 alone and/or in combination with azacitidine (Phase 1)
Timepoint [6] 0 0
On Days 1, 2, 4, 8, and 15 of Cycle 1, and on Day 1 of Cycle 2 (each cycle is 28 days)
Primary outcome [7] 0 0
Assess the Pharmacokinetics of APL-4098 alone and/or in combination with azacitidine (Phase 1)
Timepoint [7] 0 0
On Days 1, 2, 4, 8, and 15 of Cycle 1, and on Day 1 of Cycle 2 (each cycle is 28 days)
Primary outcome [8] 0 0
Assess efficacy of APL-4098 alone and/or in combination with azacitidine (Phase 2)
Timepoint [8] 0 0
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 outcome [1] 0 0
Assess response to disease with APL-4098 alone and/or in combination with azacitidine (Phase 1)
Timepoint [1] 0 0
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 outcome [2] 0 0
Duration of response with APL-4098 alone and/or in combination with azacitidine [Further efficacy] (Phase 2)
Timepoint [2] 0 0
From Cycle 1 Day 1 (a cycle is 28 days long) through end of study (approximately 2 years)
Secondary outcome [3] 0 0
Time to response with APL-4098 alone and/or in combination with azacitidine [Further efficacy] (Phase 2)
Timepoint [3] 0 0
From Cycle 1 Day 1 (a cycle is 28 days long) through end of study (approximately 2 years)
Secondary outcome [4] 0 0
Event Free Survival with APL-4098 alone and/or in combination with azacitidine [Further efficacy] (Phase 2)
Timepoint [4] 0 0
From Cycle 1 Day 1 (a cycle is 28 days long) through end of study (approximately 2 years)
Secondary outcome [5] 0 0
Overall Survival with APL-4098 alone and/or in combination with azacitidine [Further efficacy] (Phase 2)
Timepoint [5] 0 0
From Cycle 1 Day 1 (a cycle is 28 days long) through end of study (approximately 2 years)
Secondary outcome [6] 0 0
Incidence of Treatment Emergent Adverse Events [Further Safety] (Phase 2)
Timepoint [6] 0 0
Through study completion (approximately 2 years)
Secondary outcome [7] 0 0
Incidence of Adverse Events leading to discontinuation of APL-4098 [Further Tolerability] (Phase 2)
Timepoint [7] 0 0
Through study completion (approximately 2 years)
Secondary outcome [8] 0 0
Further assess the PK of APL-4098 alone and/or in combination with azacitidine (Phase 2)
Timepoint [8] 0 0
At Cycle 1 Day 1 and at Cycle 2 Day 1 (each cycle is 28 days)
Secondary outcome [9] 0 0
Further assess the PK of APL-4098 alone and/or in combination with azacitidine (Phase 2)
Timepoint [9] 0 0
At Cycle 1 Day 1 and at Cycle 2 Day 1 (each cycle is 28 days)
Secondary outcome [10] 0 0
Further assess the PK of APL-4098 alone and/or in combination with azacitidine (Phase 2)
Timepoint [10] 0 0
At Cycle 1 Day 1 and at Cycle 2 Day 1 (each cycle is 28 days)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
4/06/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/04/2027
Actual
Sample size
Target
112
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Apollo Investigative Site - Melbourne
Recruitment postcode(s) [1] 0 0
- Melbourne

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Apollo Therapeutics Ltd
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT06372717
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Daniela Pignataro, MD
Address 0 0
Apollo Therapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Apollo Therapeutics
Address 0 0
Country 0 0
Phone 0 0
781-479-2267
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06372717