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

NCT07303660 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: ZE50-0134-0004
• Study Type: interventional
• Target: 66
• Locations: 2 countries
• Sites: 6

Brief 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.

Conditions

Acute Myeloid Leukemia

Keywords

Acute Myeloid Leukemia; AML

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 24 cycles, 4 weeks each

Secondary Outcomes (5)

• Composite response rate

  Up to 24 cycles, 4 weeks each

• To determine the time to neutrophil and platelet recovery in patients receiving Lonitoclax + Aza

  Up to 24 cycles, 4 weeks each

• Overall incidence of treatment-related and non-treatment-related toxicities

  Up to 24 cycles, 4 weeks each

• Event-free survival

  Up to 24 cycles, 4 weeks each

• Duration of remission

  Up to 24 cycles, 4 weeks each

Other Outcomes (8)

• The percentage of patients that undergo hematopoietic stem cell transplant (HSCT)

  Up to 24 cycles, 4 weeks each

• Peak plasma concentration of Lonitoclax

  3 cycles, 4 weeks each

• Investigating the baseline properties of leukemia cells

  Up to 24 cycles, 4 weeks each

Study Arms (8)

ZE50-0134 + Azacitidine Dose Level -1

EXPERIMENTAL

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

Drug: Azacitidine Days 1-7; Drug: ZE 50-0134

ZE50-0134 + Azacitidine Dose Level 1

EXPERIMENTAL

Drug: ZE50-0134; Drug: Azacitidine Days 1-7

ZE50-0134 + Azacitidine Dose Level 2

EXPERIMENTAL

Drug: ZE50-0134; Drug: Azacitidine Days 1-7

ZE50-0134 + Azacitidine Dose Level 3

EXPERIMENTAL

Drug: ZE50-0134; Drug: Azacitidine Days 1-7

ZE50-0134 + Azacitidine Dose Level 4

EXPERIMENTAL

Drug: ZE50-0134; Drug: Azacitidine Days 1-7

ZE50-0134 + Azacitidine Dose Level 5

EXPERIMENTAL

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.

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.

Drug: ZE50-0134; Drug: Azacitidine Days 1-7

Interventions

ZE50-0134 DRUG

Oral capsules BID

ZE50-0134 + Azacitidine Dose Level 1; ZE50-0134 + Azacitidine Dose Level 2; ZE50-0134 + Azacitidine Dose Level 3; ZE50-0134 + Azacitidine Dose Level 4; ZE50-0134 + Azacitidine Dose Level 5; ZE50-0134 + Azacitidine Selected dose 1; ZE50-0134 + Azacitidine Selected dose 2

Azacitidine Days 1-7 DRUG

75 mg/m2 daily, days 1-7

ZE50-0134 + Azacitidine Dose Level -1; ZE50-0134 + Azacitidine Dose Level 1; ZE50-0134 + Azacitidine Dose Level 2; ZE50-0134 + Azacitidine Dose Level 3; ZE50-0134 + Azacitidine Dose Level 4; ZE50-0134 + Azacitidine Dose Level 5; ZE50-0134 + Azacitidine Selected dose 1; ZE50-0134 + Azacitidine Selected dose 2

ZE 50-0134 DRUG

Oral capsules QD

ZE50-0134 + Azacitidine Dose Level -1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.
• Isolated myeloid sarcoma (meaning, patients must have blood or marrow involvement with AML).

Sponsors & Collaborators

• Lomond Therapeutics Holdings, Inc.: lead

Study Sites (6)

State Budgetary Institution of Healthcare S.P. Botkin Moscow Multidisciplinary Scientific and Clinical Center of the Moscow Health Department

Moscow, Moscow, 125284, Russia

RECRUITING

Medsi group Joint Stock Company Clinical Hospital

Krasnogorsk, Moscow Oblast, 143442, Russia

RECRUITING

State Regional Budgetary Healthcare Institution "Novgorod Regional Clinical Hospital"

Veliky Novgorod, Novgorod Oblast, Russia

RECRUITING

Federal State Budgetary Institution "Russian Research Institute of Hematology and Transfusiology of the Federal Medical and Biological Agency"

Saint Petersburg, Sankt-Peterburg, Russia

RECRUITING

State Budgetary Healthcare Institution Leningrad Regional Clinical Hospital

Saint Petersburg, Sankt-Peterburg, Russia

RECRUITING

Republican Specialized Scientific and Practical Medical Center of Hematology of the Ministry of Health

Tashkent, 100115, Uzbekistan

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

Ekaterina Dokukina

CONTACT

+1 858 353 4108; kdokukina@eilenther.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose escalation and dose optimization study

Study Record Dates

• First Submitted: December 5, 2025
• First Posted: December 26, 2025
• Study Start: November 14, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: August 31, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

UZ (1); RU (5)