Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06366789




Registration number
NCT06366789
Ethics application status
Date submitted
5/04/2024
Date registered
16/04/2024
Date last updated
16/04/2024

Titles & IDs
Public title
Dose Escalation and Expansion Study to Evaluate the Safety, PK, PD and Efficacy of ZE46-0134 in Adults With FLT3 Mutated Relapsed or Refractory Acute Myeloid Leukemia
Scientific title
A Phase 1, Open-label, Dose Escalation and Dose Expansion, Multicenter Clinical Trial to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of ZE46-0134 in Adults With FLT3 Mutated Relapsed or Refractory Acute Myeloid Leukemia (AML)
Secondary ID [1] 0 0
CT-2024-CTN-00161-1
Secondary ID [2] 0 0
ZE46-0134-0002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
AML With Gene Mutations 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ZE46-0134

Experimental: ZE46-0134 Dose Level -1 - Optional and would only be performed Dose Level 1 is poorly tolerated

Experimental: ZE46-0134 Dose Level 1 -

Experimental: ZE46-0134 Dose Level 2 -

Experimental: ZE46-0134 Dose Level 3 -

Experimental: ZE46-0134 Dose Level 4 -

Experimental: ZE46-0134 Dose Level 5 -

Experimental: ZE46-0134 Selected dose 1 - The doses used in Part 2 of the study will be determined based on the data from Part 1 of the study and will not exceed a loading dose of 150 mg x 2 days and maintenance dose of 50 mg QD

Experimental: ZE46-0134 Selected dose 2 - The doses used in Part 2 of the study will be determined based on the data from Part 1 of the study and will not exceed a loading dose of 150 mg x 2 days and maintenance dose of 50 mg QD


Treatment: Drugs: ZE46-0134
oral capsules QD
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The incidence of DLTs
Timepoint [1] 0 0
From baseline to the End of Treatment (EOT) (Max 24 cycles, 28 days each)
Secondary outcome [1] 0 0
Incidence of AE/SAE
Timepoint [1] 0 0
From baseline to the EOT (Max 24 cycles, 28 days each)
Secondary outcome [2] 0 0
Incidence of clinically significant abnormal laboratory results
Timepoint [2] 0 0
From baseline to the EOT (Max 24 cycles, 28 days each)
Secondary outcome [3] 0 0
Incidence of abnormal clinically significant ECG results
Timepoint [3] 0 0
From baseline to the EOT (Max 24 cycles, 28 days each)
Secondary outcome [4] 0 0
Number of patients with AEs of Grade = 3
Timepoint [4] 0 0
From baseline to the EOT (Max 24 cycles, 28 days each)
Secondary outcome [5] 0 0
Number of treatment-related deaths
Timepoint [5] 0 0
From baseline to the EOT (Max 24 cycles, 28 days each)
Secondary outcome [6] 0 0
Plasma Cmax
Timepoint [6] 0 0
PK samples will be collected throughout Cycles 1 and 2 (28 days each)
Secondary outcome [7] 0 0
Plasma Css
Timepoint [7] 0 0
PK samples will be collected throughout Cycles 1 and 2 (28 days each)
Secondary outcome [8] 0 0
Plasma Cmin
Timepoint [8] 0 0
PK samples will be collected throughout Cycles 1 and 2 (28 days each)
Secondary outcome [9] 0 0
Plasma AUC
Timepoint [9] 0 0
PK samples will be collected throughout Cycles 1 and 2 (28 days each)
Secondary outcome [10] 0 0
Number of patients attaining any type of Complete Remission (CR, CRh, CRi) by Cycle 6
Timepoint [10] 0 0
Up to 6 cycles (168 days total)
Secondary outcome [11] 0 0
Number of patients attaining CR by Cycle 6
Timepoint [11] 0 0
Up to 6 cycles (168 days total)
Secondary outcome [12] 0 0
Number of patients attaining response (CR, CRh, CRi, MLFS) by Cycle 6
Timepoint [12] 0 0
Up to 6 cycles (168 days total)

Eligibility
Key inclusion criteria
* 1. Written Informed Consent must be obtained from the patient or legally authorized representative prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).

2. Patient is =18 years of age at the time of obtaining informed consent. 3. Patient is refractory to or relapsed after first-line AML therapy (with or without HSCT).

4. Patient must have a confirmed FLT3 ITD, TKD or ITD-F691L mutation documented within the past 90 days in absence of therapy or within the Screening period 28 days) prior to study drug administration on C1D1 if therapy has been given.

5. Patients must have previously been treated with Gilteritinib with failure to stop disease progression, or not met the criteria for treatment with Gilteritinib in the opinion of the Investigator, or chosen not to have treatment with Gilteritinib for social reasons.

6. Patients have a life expectancy of at least 3 months in the opinion of the Investigator.

7. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status =2.

8. Patient must meet the following criteria as indicated on the clinical laboratory tests:

a. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5 × upper limit of normal (ULN) b. Serum total bilirubin =1.5 × ULN unless due to Gilbert's disease c. Estimated glomerular filtration (eGFR) rate of >50 mL/min as calculated by the Modification of Diet in Renal Disease equation.

9. Female patients:

a. If of non-childbearing potential i.e., surgically sterilized (hysterectomy, bilateral salpingectomy, bilateral oophorectomy) at least 6 weeks before the Screening visit or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause and a follicle-stimulating hormone (FSH) level consistent with postmenopausal status, per local laboratory guidelines), or b. If of childbearing potential, must: i. Have a negative serum pregnancy test at the Screening visit and urine pregnancy test on admission to the clinic on Day-1.

ii. Agree not to attempt to become pregnant or donate ova from signing the consent form until at least 45 days after the last dose of study drug.

iii. Agree to use adequate contraception (defined as use of a condom by the male partner combined with use of a highly effective method of contraception from Screening until at least 45 days after the last dose of study drug, if not exclusively in a same-sex relationship or abstinent as a committed lifestyle).

10. Male patients and their female spouse/partners who are of childbearing potential must agree to use highly effective contraception consisting of 2 forms of birth control (at least 1of which must be a barrier method) starting at Screening and continue throughout the study period and for 45 days after the final study drug administration. Male patient must not donate sperm starting at Screening and throughout the study period and for 45 days after the final study drug administration.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Written Informed Consent must be obtained from the patient or legally authorized representative prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).
2. Patient is =18 years of age at the time of obtaining informed consent.
3. Patient is refractory to or relapsed after first-line AML therapy (with or without HSCT).
4. Patient must have a confirmed FLT3 ITD, TKD or ITD-F691L mutation documented within the past 90 days in absence of therapy or within the Screening period 28 days) prior to study drug administration on C1D1 if therapy has been given.
5. Patients must have previously been treated with Gilteritinib with failure to stop disease progression, or not met the criteria for treatment with Gilteritinib in the opinion of the Investigator, or chosen not to have treatment with Gilteritinib for social reasons.
6. Patients have a life expectancy of at least 3 months in the opinion of the Investigator.
7. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status =2.
8. Patient must meet the following criteria as indicated on the clinical laboratory tests:

1. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5 × upper limit of normal (ULN)
2. Serum total bilirubin =1.5 × ULN unless due to Gilbert's disease
3. Estimated glomerular filtration (eGFR) rate of >50 mL/min as calculated by the Modification of Diet in Renal Disease equation.
9. Female patients:

1. If of non-childbearing potential i.e., surgically sterilized (hysterectomy, bilateral salpingectomy, bilateral oophorectomy) at least 6 weeks before the Screening visit or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause and a follicle-stimulating hormone (FSH) level consistent with postmenopausal status, per local laboratory guidelines), or
2. If of childbearing potential, must:

i. Have a negative serum pregnancy test at the Screening visit and urine pregnancy test on admission to the clinic on Day-1.

ii. Agree not to attempt to become pregnant or donate ova from signing the consent form until at least 45 days after the last dose of study drug.

iii. Agree to use adequate contraception (defined as use of a condom by the male partner combined with use of a highly effective method of contraception from Screening until at least 45 days after the last dose of study drug, if not exclusively in a same-sex relationship or abstinent as a committed lifestyle).
10. Male patients and their female spouse/partners who are of childbearing potential must agree to use highly effective contraception consisting of 2 forms of birth control (at least 1of which must be a barrier method) starting at Screening and continue throughout the study period and for 45 days after the final study drug administration. Male patient must not donate sperm starting at Screening and throughout the study period and for 45 days after the final study drug administration.

Exclusion criteria

1. Diagnosis of isolated myeloid sarcoma (meaning, patients must have blood or marrow involvement with AML)
2. Acute promyelocytic leukemia (FAB M3)
3. Active central nervous system (CNS) involvement by AML
4. Clinical signs/symptoms of leukostasis requiring urgent therapy
5. Known active infection with Human Immunodeficiency Virus (HIV), hepatitis B or hepatitis C. Patients with a history of positive serology for hepatitis B or C require a negative Polymerase chain reaction (PCR) test for virus to go onto therapy
6. Disseminated intravascular coagulopathy with active, unmanageable bleeding or signs of thrombosis.
7. Patients who have received an investigational agent (for any indication) within 5 half-lives of the agent; if the half-life of the agent is unknown, patients must wait 1 week prior to first dose of study treatment. An investigational agent is one for which there is no approved indication by the local regulatory authority.
8. Systemic antineoplastic therapy within 5 half-lives or radiation therapy within 1 week prior to starting protocol with the exception of hydroxyurea, which is allowed to control white blood cell counts.
9. Female patients who are pregnant or lactating
10. Patients with psychological, familial, social, or geographic factors, other significant medical condition, laboratory abnormality that otherwise preclude them from giving informed consent, following the protocol, potentially hamper compliance with study treatment and follow-up or would confound the interpretation of the results of the study.
11. Patients with the following will be excluded: uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, myocardial infarction with evidence of residual abnormalities within 6 months prior to enrollment (Troponin (regular or high sensitivity) leak alone not included if no residual dysfunction), New York Heart Association (NYHA) Class III or IV heart failure, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Patients with medical comorbidities that will preclude safety evaluation of the combination should not be enrolled.
12. Infection is a common feature of AML, patients with active infection are permitted to enroll provided that the infection is under control in the opinion of the Investigator. Patients with uncontrolled infection shall not be enrolled until infection is treated and brought under control.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
1/04/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2027
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Nedlands, W
Recruitment hospital [1] 0 0
Linear Clinical Research Ltd - Perth
Recruitment postcode(s) [1] 0 0
6009 - Perth

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Carolyn Grove, Prof
Address 0 0
Linear Clinical Research
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Kate Dokukina, PhD, MD
Address 0 0
Country 0 0
Phone 0 0
+38269728309
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT06366789