A Phase 1b Study of Lonitoclax + Azacitidine in Acute Myeloid Leukemia Patients

NCT ID: NCT07303660

Last Updated: 2025-12-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

66 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-01-10

Study Completion Date

2027-11-30

Brief Summary

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This is a clinical study aiming to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of ZE50-0134 in relapsed and refractory Acute Myeloid Leukemia patients.

Detailed Description

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It is an open-label Phase 1b clinical study of Lonitoclax + Aza in relapsed/refractory AML patients. The study is an open-label, with 2 parts.

The phase 1b dose escalation portion would include relapsed/refractory patients, as well as in the expansion group. Once the phase 1b dose and schedule of Lonitoclax + Aza is defined in the 3 + 3 design with biologically effective dose assessment, an amendment will be filed with the Regulatory Authorities and expansion cohort of 30 relapsed and refractory AML patients would be enrolled at two different doses (15 patients per dose) to determine the RP2D; the first dosing will be at the presumed potential phase 2 dose combination and the second dosing will be below this.

Conditions

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Acute Myeloid Leukemia

Keywords

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Acute Myeloid Leukemia AML

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Dose escalation and dose optimization study
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ZE50-0134 + Azacitidine Dose Level -1

Optional and would only be performed Dose Level 1 is poorly tolerated.

Group Type EXPERIMENTAL

Azacitidine Days 1-7

Intervention Type DRUG

75 mg/m2 daily, days 1-7

ZE 50-0134

Intervention Type DRUG

Oral capsules QD

ZE50-0134 + Azacitidine Dose Level 1

Group Type EXPERIMENTAL

ZE50-0134

Intervention Type DRUG

Oral capsules BID

Azacitidine Days 1-7

Intervention Type DRUG

75 mg/m2 daily, days 1-7

ZE50-0134 + Azacitidine Dose Level 2

Group Type EXPERIMENTAL

ZE50-0134

Intervention Type DRUG

Oral capsules BID

Azacitidine Days 1-7

Intervention Type DRUG

75 mg/m2 daily, days 1-7

ZE50-0134 + Azacitidine Dose Level 3

Group Type EXPERIMENTAL

ZE50-0134

Intervention Type DRUG

Oral capsules BID

Azacitidine Days 1-7

Intervention Type DRUG

75 mg/m2 daily, days 1-7

ZE50-0134 + Azacitidine Dose Level 4

Group Type EXPERIMENTAL

ZE50-0134

Intervention Type DRUG

Oral capsules BID

Azacitidine Days 1-7

Intervention Type DRUG

75 mg/m2 daily, days 1-7

ZE50-0134 + Azacitidine Dose Level 5

Group Type EXPERIMENTAL

ZE50-0134

Intervention Type DRUG

Oral capsules BID

Azacitidine Days 1-7

Intervention Type DRUG

75 mg/m2 daily, days 1-7

ZE50-0134 + Azacitidine 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.

Group Type EXPERIMENTAL

ZE50-0134

Intervention Type DRUG

Oral capsules BID

Azacitidine Days 1-7

Intervention Type DRUG

75 mg/m2 daily, days 1-7

ZE50-0134 + Azacitidine 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.

Group Type EXPERIMENTAL

ZE50-0134

Intervention Type DRUG

Oral capsules BID

Azacitidine Days 1-7

Intervention Type DRUG

75 mg/m2 daily, days 1-7

Interventions

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ZE50-0134

Oral capsules BID

Intervention Type DRUG

Azacitidine Days 1-7

75 mg/m2 daily, days 1-7

Intervention Type DRUG

ZE 50-0134

Oral capsules QD

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1\. Patients must be able to understand and provide written informed consent. 2. AML patients: For the dose escalation and expansion, patients aged 18 and older with relapsed and/or refractory AML would be eligible. Prior treatment with a hypomethylating agent or Venetoclax is allowed.

3\. At the time of Lonitoclax initiation, white blood count (WBC) needs to be \< 25 × 109/L: Hydroxyurea can be used to achieve that level.

4\. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2. 5. Adequate organ function as defined by the following:

1. Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN), alanine aminotransferase (ALT) ≤ 2.5 x ULN. AST and/or ALT may be up to 5 x ULN if thought to be secondary to leukemia.
2. Total bilirubin ≤ 1.5 x ULN (patients with known Gilbert's syndrome may enroll if direct bilirubin is ≤ 3 x ULN) for the local laboratory.
3. Estimated Glomerular Filtration Rate (eGFR) according to the Chronic Kidney Disease Epidemiology Collaboration (CDK-EPI) ≥ 60 mL/min/1.73m2 for the local laboratory.

6\. Female patients of childbearing potential must agree to use a highly effective method of contraception from screening visit until 120 days following the last dose of study treatment. Highly effective methods of contraception include sexual abstinence, bilateral tubal ligation, tricycle combined (estrogen and progestogen containing) oral or transdermal hormonal contraceptives, intrauterine devices and vasectomized partner. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately.

7\. Male patients capable of having intercourse with females of childbearing potential must agree to abstain from heterosexual intercourse or have their partner use highly effective contraception from the screening visit until 120 days until the last dose of study treatment, and themselves use barrier contraception (i.e., condoms). They must also refrain from sperm donation from the screening visit until 120 days following the last dose of study treatment. Should his partner become pregnant or suspect she is pregnant while he is participating in this study, he should inform his treating physician immediately.

Exclusion Criteria

1. 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 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 Regulatory Authorities.
8. Systemic antineoplastic therapy within 1 week (or 5 half-lives of drug received, whichever is shorter) or radiation therapy within 1 week prior to starting protocol except for 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 trial.
11. Concomitant medications that are strong CYP3A4 inducers.
12. Patients with QTcF \> 470 msec that cannot be corrected with electrolyte replacement, hydration, or medication modifications. This does not apply to patients with a pacemaker as measurement of QTc is not accurate under such conditions and bears no risk to patients since they are being medically paced by their device.
13. 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 leak alone not included if no residual dysfunction), familial QT prolongation, known potassium wasting syndrome (Bartter syndrome, Gitelman syndrome, and Liddle syndrome), New York Heart Association (NYHA) Class III or IV heart failure, 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.
14. As infection is a common feature of AML, patients with active infection are permitted to enroll provided that the infection is under control. Patients with uncontrolled infection shall not be enrolled until infection is treated and brought under control.

1. 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 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 Regulatory Authorities.
8. Systemic antineoplastic therapy within 1 week (or 5 half-lives of drug received, whichever is shorter) or radiation therapy within 1 week prior to starting protocol except for 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 trial.
11. Concomitant medications that are strong CYP3A4 inducers.
12. Patients with QTcF \> 470 msec that cannot be corrected with electrolyte replacement, hydration, or medication modifications. This does not apply to patients with a pacemaker as measurement of QTc is not accurate under such conditions and bears no risk to patients since they are being medically paced by their device.
13. 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 leak alone not included if no residual dysfunction), familial QT prolongation, known potassium wasting syndrome (Bartter syndrome, Gitelman syndrome, and Liddle syndrome), New York Heart Association (NYHA) Class III or IV heart failure, 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.
14. As infection is a common feature of AML, patients with active infection are permitted to enroll provided that the infection is under control. Patients with uncontrolled infection shall not be enrolled until infection is treated and brought under control.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Lomond Therapeutics Holdings, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Central Contacts

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Ekaterina Dokukina

Role: CONTACT

Phone: +38269728309

Email: [email protected]

Other Identifiers

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ZE50-0134-0004

Identifier Type: -

Identifier Source: org_study_id