Health Trials

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

ConditionAcute Myeloid Leukemia
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorLomond Therapeutics Holdings, Inc.

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Sequential

Treatments tested in this trial

  • ZE50-0134

    Drug

    Oral capsules BID

  • Azacitidine Days 1-7

    Drug

    75 mg/m2 daily, days 1-7

  • ZE 50-0134

    Drug

    Oral capsules QD

Treatment groups

66 Participants
are divided into 8 treatment groups

8

Treatment groups

See each treatment group below.

Group A: ZE50-0134 + Azacitidine Dose Level -1Experimental treatment 2 interventions
Group B: ZE50-0134 + Azacitidine Dose Level 1Experimental treatment 2 interventions
Group C: ZE50-0134 + Azacitidine Dose Level 2Experimental treatment 2 interventions
Group D: ZE50-0134 + Azacitidine Dose Level 3Experimental treatment 2 interventions
Group E: ZE50-0134 + Azacitidine Dose Level 4Experimental treatment 2 interventions
Group F: ZE50-0134 + Azacitidine Dose Level 5Experimental treatment 2 interventions
Group G: ZE50-0134 + Azacitidine Selected dose 1Experimental treatment 2 interventions
Group H: ZE50-0134 + Azacitidine Selected dose 2Experimental treatment 2 interventions

Trial outcomes

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.

Time frame
Up to 24 cycles, 4 weeks each

Secondary outcomes

1

Composite response rate

Composite response rate will be defined as the proportion of efficacy-evaluable patients who achieve CR, CRi, CRh, or MLFS.

Time frame
Up to 24 cycles, 4 weeks each
2

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

Monitoring of neutrophil and platelet counts

Time frame
Up to 24 cycles, 4 weeks each
3

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

To determine the overall incidence of treatment-related and non-treatment-related toxicities.

Time frame
Up to 24 cycles, 4 weeks each
4

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.

Time frame
Up to 24 cycles, 4 weeks each

Other outcomes

1

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

To determine the percentage of patients that undergo hematopoietic stem cell transplant (HSCT).

Time frame
Up to 24 cycles, 4 weeks each
2

Peak plasma concentration of Lonitoclax

To determine peak plasma concentration of Lonitoclax when dosed in combination with Aza and its interaction with strong CYP3A4 inhibitors used in this disease

Time frame
3 cycles, 4 weeks each
3

Investigating the baseline properties of leukemia cells

To examine the baseline properties of leukemia cells that respond versus those that do not respond to initial therapy.

Time frame
Up to 24 cycles, 4 weeks each
4

Serial properties of AML cells

To determine the serial properties of AML cells that respond and then become resistant to this novel combination.

Time frame
Up to 24 cycles, 4 weeks each

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Lomond Therapeutics Holdings, Inc.

Lead sponsor

Source ClinicalTrials.gov
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