Acute Myeloid LeukemiaPhase 1NCT07303660
A Phase 1b Study of Lonitoclax + Azacitidine in Acute Myeloid Leukemia Patients
A Phase 1 study testing ZE50-0134, Azacitidine Days 1-7 and ZE 50-0134 in people with Acute Myeloid Leukemia, run by Lomond Therapeutics Holdings, Inc. at 6 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- ZE50-0134, Azacitidine Days 1-7 and ZE 50-0134
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 6 sitesin 2 countries
- Study dates
- 14 Nov 2025to Jul 2027
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- 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.
- 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.
- Estimated Glomerular Filtration Rate (eGFR) according to the Chronic Kidney Disease Epidemiology Collaboration (CDK-EPI) ≥ 60 mL/min/1.73m2 for the local laboratory.
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- 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.
- 8. Patients must be able to take oral medications. Exclusion Criteria
- Isolated myeloid sarcoma (meaning, patients must have blood or marrow involvement with AML).
- Acute promyelocytic leukemia (FAB M3).
- Active central nervous system (CNS) involvement by AML.
- Clinical signs/symptoms of leukostasis requiring urgent therapy.
- 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.
- Disseminated intravascular coagulopathy with active bleeding or signs of thrombosis
- 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.
- 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.
- Female patients who are pregnant or lactating.
- 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.
- Concomitant medications that are strong CYP3A4 inducers.
- 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.
- 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.
- 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.
Who cannot join
- Isolated myeloid sarcoma (meaning, patients must have blood or marrow involvement with AML).
- Acute promyelocytic leukemia (FAB M3).
- Active central nervous system (CNS) involvement by AML.
- Clinical signs/symptoms of leukostasis requiring urgent therapy.
- 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.
- Disseminated intravascular coagulopathy with active bleeding or signs of thrombosis
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- 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.
- 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.
- Female patients who are pregnant or lactating.
- 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.
- Concomitant medications that are strong CYP3A4 inducers.
- 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.
- 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.
- 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.
Trial locations and contacts
6 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
6 sites in 2 countries
Russia5 sites, 5 recruiting
- Recruiting
Medsi group Joint Stock Company Clinical Hospital
Krasnogorsk, Moscow Oblast, 143442
- Recruiting
State Budgetary Institution of Healthcare S.P. Botkin Moscow Multidisciplinary Scientific and Clinical Center of the Moscow Health Department
Moscow, Moscow, 125284
- Recruiting
Federal State Budgetary Institution "Russian Research Institute of Hematology and Transfusiology of the Federal Medical and Biological Agency"
Saint Petersburg, Sankt-Peterburg
- Recruiting
State Budgetary Healthcare Institution Leningrad Regional Clinical Hospital
Saint Petersburg, Sankt-Peterburg
- Recruiting
State Regional Budgetary Healthcare Institution "Novgorod Regional Clinical Hospital"
Velikiy Novgorod, Novgorod Oblast
Uzbekistan1 site, 1 recruiting
- Recruiting
Republican Specialized Scientific and Practical Medical Center of Hematology of the Ministry of Health
Tashkent, 100115
About this study
Official title: A Phase 1b Study of Lonitoclax + Azacitidine (Aza) in Acute Myeloid Leukemia (AML) Patients
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.
Read the detailed description
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
- Acute Myeloid Leukemia
- Being tested
- ZE50-0134, Azacitidine Days 1-7, ZE 50-0134
- Keywords
- Acute Myeloid Leukemia, AML
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZE50-0134Drug
Oral capsules BID
Azacitidine Days 1-7Drug
75 mg/m2 daily, days 1-7
ZE 50-0134Drug
Oral capsules QD
| Study group | Role | What they receive |
|---|---|---|
| ZE50-0134 + Azacitidine Dose Level -1 | Experimental | Optional and would only be performed Dose Level 1 is poorly tolerated. Receives: Drug: Azacitidine Days 1-7; Drug: ZE 50-0134 |
| ZE50-0134 + Azacitidine Dose Level 1 | Experimental | Not described Receives: Drug: ZE50-0134; Drug: Azacitidine Days 1-7 |
| ZE50-0134 + Azacitidine Dose Level 2 | Experimental | Not described Receives: Drug: ZE50-0134; Drug: Azacitidine Days 1-7 |
| ZE50-0134 + Azacitidine Dose Level 3 | Experimental | Not described Receives: Drug: ZE50-0134; Drug: Azacitidine Days 1-7 |
| ZE50-0134 + Azacitidine Dose Level 4 | Experimental | Not described Receives: Drug: ZE50-0134; Drug: Azacitidine Days 1-7 |
| ZE50-0134 + Azacitidine Dose Level 5 | Experimental | Not described Receives: Drug: ZE50-0134; Drug: Azacitidine Days 1-7 |
| ZE50-0134 + Azacitidine Selected dose 1 | Experimental | The doses used in Part 2 of the study will be determined based on the data from Part 1 of the study. Receives: Drug: ZE50-0134; Drug: Azacitidine Days 1-7 |
| ZE50-0134 + Azacitidine Selected dose 2 | Experimental | The doses used in Part 2 of the study will be determined based on the data from Part 1 of the study. Receives: Drug: ZE50-0134; Drug: Azacitidine Days 1-7 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determination of the RP2D and expansion cohort enrollment
To determine the recommended phase 2 (RP2D) dose using a 28-day schedule in relapsed and refractory (R/R) AML followed by an expansion cohort.
Measured: Up to 24 cycles, 4 weeks each
Secondary outcomes (5)
Composite response rate
Composite response rate will be defined as the proportion of efficacy-evaluable patients who achieve CR, CRi, CRh, or MLFS.
Measured: Up to 24 cycles, 4 weeks each
To determine the time to neutrophil and platelet recovery in patients receiving Lonitoclax + Aza
Monitoring of neutrophil and platelet counts
Measured: Up to 24 cycles, 4 weeks each
Overall incidence of treatment-related and non-treatment-related toxicities
To determine the overall incidence of treatment-related and non-treatment-related toxicities.
Measured: Up to 24 cycles, 4 weeks each
Event-free survival
Event-free survival will be measured from start of the treatment to the first of failure to achieve a CR/CRi/CRh/MLFS, or relapse, or death due to any cause, with patients last known to be alive and event-free censored at the date of last contact.
Measured: Up to 24 cycles, 4 weeks each
Duration of remission
Duration of remission is defined in responders as the time from documentation of remission to the date of disease progression.
Measured: Up to 24 cycles, 4 weeks each
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2025
- Study start14 Nov 2025
- Primary completionDec 2026 (estimated)
- Study completionJul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Dose escalation and dose optimization study
- Masking
- None (open label)
- Enrolment
- 66 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Lomond Therapeutics Holdings, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07303660
- Sponsor's protocol ID
- ZE50-0134-0004
- Status last verified
- Aug 2026
- First submitted
- 5 Dec 2025
- Last updated
- 31 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No