CLL / SLLPhase 1NCT06708897
A Study of Lonitoclax (ZE50-0134) in Relapsed or Refractory B-cell Malignancies
A Phase 1 study testing Lonitoclax (ZE50-0134) in people with CLL / SLL and CLL (Chronic Lymphocytic Leukemia), run by Lomond Therapeutics Holdings, Inc. at 5 sites in United States.
Trial summary
This Phase 1, open-label, multicenter study is evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of lonitoclax (ZE50-0134) in adults with relapsed or refractory chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and select low-grade B-cell… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- CLL / SLL, CLL (Chronic Lymphocytic Leukemia), SLL (Small Lymphocytic Lymphoma)
- What is being tested?
- Lonitoclax (ZE50-0134)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 84 participants
- Where
- 5 sitesUnited States
- Study dates
- 8 Apr 2025to Jul 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- Men and women aged 18 years or older.
- Disease as defined below:
- Part 1: Relapsed or refractory CLL or SLL, as defined by iwCLL, after at least 2 prior therapies that included a covalent Bruton tyrosine kinase inhibitor (BTKi) and venetoclax, or after the participant declined venetoclax; or progressive low-grade lymphoma, including marginal zone lymphoma or lymphoplasmacytic lymphoma (including Waldenstrom macroglobulinemia), after at least 1 prior therapy that included either a BTKi or CD20 antibody-based therapy.
- Part 2: Relapsed or refractory CLL or SLL, as defined by iwCLL, after at least 1 prior therapy that included a BTKi; participants must be venetoclax naive.
- Disease requiring therapy in the investigator's opinion.
- Adequate bone marrow, liver, and renal function during screening:
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- Absolute neutrophil count greater than 0.75 x 10^9/L; for participants with documented bone marrow involvement, at least 0.5 x 10^9/L.
- Platelet count greater than 50 x 10^9/L; for participants with documented bone marrow involvement, at least 30 x 10^9/L.
- AST and ALT no greater than 3.0 times the upper limit of normal.
- Total bilirubin no greater than 1.5 times the upper limit of normal. Participants with suspected or known Gilbert disease may have total bilirubin up to 3 times the upper limit of normal if predominantly unconjugated.
- Creatinine- or cystatin C-based glomerular filtration rate at least 60 mL/min, or at least 40 mL/min with a normal urine neutrophil gelatinase-associated lipocalin level. Estimated GFR is calculated using the Modification of Diet in Renal Disease formula.
- Eastern Cooperative Oncology Group performance status of 0, 1, or 2.
- For women of childbearing potential, a negative serum or urine pregnancy test within 7 days before the first dose and a negative result before each treatment cycle. Pregnancy testing is not required for women older than 50 years with at least 12 months of amenorrhea; women aged 50 years or younger with at least 6 months of spontaneous amenorrhea and follicle-stimulating hormone greater than 40 mIU/mL; or permanently sterilized women, including hysterectomy, bilateral salpingectomy, or uterine ablation.
- Women and men of reproductive potential must agree to use highly effective contraception from signing informed consent until 90 days after the last dose of study drug.
- Ability to understand and willingness to sign written informed consent, including consent for genetic biomarker analyses from tissue and plasma, before study-specific procedures.
Who cannot join
- Part 2 only: Prior venetoclax treatment.
- Known active Richter transformation. Participants previously treated for Richter transformation may be eligible if they have been in remission for more than 2 years, have no evidence of Richter transformation, and have CLL only.
- Known hypersensitivity to lonitoclax, its excipients, or an agent administered in association with the study.
- Clinically significant cardiac disease, including congestive heart failure greater than New York Heart Association Class II; uncontrolled coronary artery disease; unstable angina; new-onset angina or myocardial infarction within 6 months before first dose; major regional wall-motion abnormalities on baseline echocardiography; or cardiac arrhythmias requiring antiarrhythmic treatment other than beta-blockers or digoxin.
- Known active cytomegalovirus, hepatitis B virus, or hepatitis C virus infection.
- HIV-positive disease that is not adequately controlled by antiviral therapy. Participants with adequately controlled HIV may enroll.
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- Known active SARS-CoV-2 infection. Prior infection is allowed if the participant completely recovered more than 14 days previously.
- Active clinically serious infection of Grade greater than 2 requiring parenteral therapy. Participants may be eligible after the infection resolves.
- Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura within 28 days before enrollment.
- Allogeneic bone marrow transplant within 4 months before first dose. Immunosuppressive therapy related to the transplant must be completed before enrollment.
- Active cancer that limits expected survival to less than 2 years or requires anticancer therapy concomitantly with study treatment. Exceptions may include resected localized skin, breast, or prostate cancer and malignancies treated with hormonal or immune therapies alone; secondary cancers should be discussed with the Medical Monitor.
- Physical examination or laboratory finding that contraindicates investigational therapy or otherwise places the participant at excessively high treatment risk in the investigator's opinion.
- Requirement for ongoing immunosuppressive therapy, including systemic corticosteroids, for cancer or another condition. Topical or inhaled corticosteroids and low-dose systemic steroids of no more than 20 mg prednisone equivalent per day are permitted for comorbid conditions. Short courses above this dose before first dose and during Week 1 may be used for tumor flare.
- Major surgery or significant trauma within 4 weeks before first dose.
- Breastfeeding. Breastfeeding must be discontinued before and during treatment and for at least 3 months after treatment ends.
- QT interval corrected using Fridericia's formula greater than 470 milliseconds that cannot be corrected with electrolyte replacement, hydration, or medication modification. This criterion does not apply to participants with a pacemaker.
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
United States5 sites, 5 recruiting
- Recruiting
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
- Recruiting
University of Cincinnati
Cincinnati, Ohio, 45221
- Recruiting
The Ohio State University
Columbus, Ohio, 43210
- Not yet recruiting
UT Southwestern Medical Center
Dallas, Texas, 75390
- Recruiting
Norton Cancer Institute, St. Matthews Campus
Louisville, Kentucky, 40207
About this study
Official title: Phase 1 Study of Lonitoclax (ZE50-0134) in Relapsed and Refractory Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL), and Select Low-grade Lymphomas
This Phase 1, open-label, multicenter study is evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of lonitoclax (ZE50-0134) in adults with relapsed or refractory chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and select low-grade B-cell lymphomas.
The study has two sequential parts. Part 1 uses dose escalation to determine the biologically effective dose and/or maximum tolerated dose of lonitoclax. Participants receive a 3-day step-up regimen followed by continuous once-daily or twice-daily oral dosing in 28-day cycles. Part 2 is a randomized dose-expansion comparison of two selected lonitoclax dose levels in venetoclax-naive participants with relapsed or refractory CLL/SLL. Treatment may continue for up to 12 cycles and, for participants deriving clinical benefit, for up to 24 cycles with approval from the Medical Monitor.
Read the detailed description
This is an open-label, multicenter Phase 1 study with two sequential parts.
Part 1 is a non-randomized dose-escalation study in participants with relapsed or refractory CLL/SLL or select low-grade lymphomas. A standard 3+3 design is used to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of lonitoclax (ZE50-0134), and to identify a biologically effective dose and/or maximum tolerated dose. Planned dose levels include once-daily and twice-daily regimens. Dose Levels 6a and 6b may enroll concurrently. Dose-limiting toxicities are evaluated during Cycle 1.
To reduce the risk of tumor lysis syndrome, participants receive intravenous hydration beginning on Day -1 and a 3-day step-up dosing regimen as inpatients. After step-up dosing, the assigned lonitoclax dose is administered orally once daily or twice daily in a fed state. Each treatment cycle is 28 days.
Part 2 is a randomized dose-expansion portion in venetoclax-naive participants with relapsed or refractory CLL/SLL. Approximately 15 participants are assigned to each of two selected dose levels: the biologically effective dose or maximum tolerated dose and one lower dose level, provided activity is observed. Part 2 evaluates safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity to support selection of a recommended Phase 2 dose.
Treatment is continuous for up to 12 cycles. Participants deriving clinical benefit may continue treatment for up to 24 cycles at the investigator's discretion with Medical Monitor approval. Participants are followed for safety after treatment and for disease progression, subsequent treatment, and survival.
- Conditions
- CLL / SLL, CLL (Chronic Lymphocytic Leukemia), SLL (Small Lymphocytic Lymphoma), Marginal Zone Lymphoma(MZL), Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia
- Being tested
- Lonitoclax (ZE50-0134)
- Keywords
- Lonitoclax, ZE50-0134, BCL2 inhibitor, relapsed or refractory, dose escalation, dose expansion, dose optimization, BTK inhibitor, venetoclax, tumor lysis syndrome
- Medical subject headings
- Leukemia, B-Cell, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, B-Cell, Marginal Zone, Waldenstrom Macroglobulinemia, Recurrence, Tumor Lysis Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lonitoclax (ZE50-0134)Drug
Lonitoclax is supplied as immediate-release white opaque soft gelatin capsules in 25 mg, 100 mg, and 250 mg strengths. Participants receive a 3-day step-up regimen followed by the assigned oral dose once daily (QD) or twice daily (BID) in a fed state, administered within 1 hour of food. Each cycle is 28 days. Treatment continues for up to 12 cycles and may continue for up to 24 cycles in participants deriving clinical benefit, at the investigator's discretion with Medical Monitor approval. Participants receive inpatient monitoring and tumor lysis syndrome prophylaxis during the initial step-up period.
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Dose Level -1 - 75 mg QD | Experimental | Optional de-escalation cohort. Participants receive lonitoclax 25 mg once daily on Day 1, 50 mg once daily on Day 2, and 75 mg once daily on Day 3 and thereafter. Treatment is administered orally in a fed state in 28-day cycles. Receives: Drug: Lonitoclax (ZE50-0134) |
| Part 1: Dose Level 1 - 100 mg QD | Experimental | Participants receive lonitoclax 25 mg once daily on Day 1, 50 mg once daily on Day 2, and 100 mg once daily on Day 3 and thereafter. Treatment is administered orally in a fed state in 28-day cycles. Receives: Drug: Lonitoclax (ZE50-0134) |
| Part 1: Dose Level 2 - 200 mg QD | Experimental | Participants receive lonitoclax 50 mg once daily on Day 1, 100 mg once daily on Day 2, and 200 mg once daily on Day 3 and thereafter. Treatment is administered orally in a fed state in 28-day cycles. Receives: Drug: Lonitoclax (ZE50-0134) |
| Part 1: Dose Level 3 - 400 mg QD | Experimental | Participants receive lonitoclax 50 mg once daily on Day 1, 100 mg once daily on Day 2, and 400 mg once daily on Day 3 and thereafter. Treatment is administered orally in a fed state in 28-day cycles. Receives: Drug: Lonitoclax (ZE50-0134) |
| Part 1: Dose Level 4 - 600 mg QD | Experimental | Participants receive lonitoclax 50 mg once daily on Day 1, 100 mg once daily on Day 2, and 600 mg once daily on Day 3 and thereafter. Treatment is administered orally in a fed state in 28-day cycles. Receives: Drug: Lonitoclax (ZE50-0134) |
| Part 1: Dose Level 5 - 800 mg QD | Experimental | Participants receive lonitoclax 50 mg once daily on Day 1, 100 mg once daily on Day 2, and 800 mg once daily on Day 3 and thereafter. Treatment is administered orally in a fed state in 28-day cycles. Receives: Drug: Lonitoclax (ZE50-0134) |
| Part 1: Dose Level 6a - 1000 mg QD | Experimental | Participants receive lonitoclax 100 mg once daily on Day 1, 250 mg once daily on Day 2, and 1000 mg once daily on Day 3 and thereafter. Treatment is administered orally in a fed state in 28-day cycles. Dose Levels 6a and 6b may enroll concurrently. Receives: Drug: Lonitoclax (ZE50-0134) |
| Part 1: Dose Level 6b - 500 mg BID | Experimental | Participants receive lonitoclax 50 mg twice daily on Day 1, 100 mg twice daily on Day 2, and 500 mg twice daily on Day 3 and thereafter. Treatment is administered orally in a fed state in 28-day cycles. Dose Levels 6a and 6b may enroll concurrently. Receives: Drug: Lonitoclax (ZE50-0134) |
| Part 1: Dose Level 7b - 750 mg BID | Experimental | Participants receive lonitoclax 100 mg twice daily on Day 1, 250 mg twice daily on Day 2, and 750 mg twice daily on Day 3 and thereafter. Treatment is administered orally in a fed state in 28-day cycles. Receives: Drug: Lonitoclax (ZE50-0134) |
| Part 1: Dose Level 8b - 1000 mg BID | Experimental | Participants receive lonitoclax 100 mg twice daily on Day 1, 250 mg twice daily on Day 2, and 1000 mg twice daily on Day 3 and thereafter. Treatment is administered orally in a fed state in 28-day cycles. Receives: Drug: Lonitoclax (ZE50-0134) |
| Part 2: Selected Dose A - BED/MTD | Experimental | Participants with relapsed or refractory CLL/SLL who are venetoclax naive are randomized to a selected lonitoclax dose corresponding to the biologically effective dose or maximum tolerated dose identified in Part 1. The selected regimen may be once daily or twice daily. Approximately 15 participants are planned. Receives: Drug: Lonitoclax (ZE50-0134) |
| Part 2: Selected Dose B - One Dose Level Lower | Experimental | Participants with relapsed or refractory CLL/SLL who are venetoclax naive are randomized to one lonitoclax dose level below the biologically effective dose or maximum tolerated dose selected in Part 1, provided activity is observed. The selected regimen may be once daily or twice daily. Approximately 15 participants are planned. Receives: Drug: Lonitoclax (ZE50-0134) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and severity of treatment-emergent adverse events and serious adverse events
Number and percentage of participants with treatment-emergent adverse events, serious adverse events, clinically significant laboratory abnormalities, adverse events related to lonitoclax, and adverse events leading to treatment discontinuation. Adverse events are graded using NCI CTCAE Version 5.0.
Measured: From first dose through 30 days after the last dose; treatment may continue for up to 24 cycles (28 days per cycle).
Incidence of dose-limiting toxicities in Part 1
Number and percentage of Part 1 participants experiencing a protocol-defined dose-limiting toxicity during the dose-limiting toxicity assessment period.
Measured: Cycle 1 (Days 1-28).
Determination of the biologically effective dose and/or maximum tolerated dose
The selected dose is determined from the totality of safety, dose-limiting toxicity, pharmacokinetic, pharmacodynamic, and early response data across Part 1 dose cohorts according to the protocol-defined dose-escalation rules.
Measured: After completion of Cycle 1 for evaluable participants in each Part 1 dose cohort.
Secondary outcomes (6)
Overall Response Rate (ORR)
Proportion of participants whose best overall response is partial response or better, as assessed by the investigator using iwCLL criteria for CLL, Lugano criteria for SLL and other applicable low-grade lymphomas, or Waldenstrom response criteria, as applicable.
Measured: From first dose through end of treatment, up to 24 cycles (28 days per cycle).
Duration of response (DOR)
For participants with partial response or better, time from the first documented response until disease progression or death from any cause.
Measured: From first documented response until progression, death, withdrawal, loss to follow-up, or sponsor termination; assessed during treatment and long-term follow-up.
Progression-free survival (PFS)
Time from first dose until disease progression by the applicable disease-specific response criteria or death from any cause.
Measured: From first dose until progression, death, withdrawal, loss to follow-up, or sponsor termination; assessed during treatment and long-term follow-up.
Time to next treatment (TTNT)
Time from first dose of lonitoclax to initiation of a non-protocol anticancer treatment for CLL/SLL or death.
Measured: From first dose until initiation of new anticancer treatment, death, withdrawal, loss to follow-up, or sponsor termination.
Maximum observed plasma concentration (Cmax) of lonitoclax
Maximum observed plasma concentration derived from serial plasma concentration measurements after lonitoclax administration.
Measured: Cycle 1 Days 1-4, 8, 15, and 22; Cycle 2 Days 1-2; and end-of-treatment/early-termination sampling as applicable.
Area under the plasma concentration-time curve (AUC) of lonitoclax
AUC derived from serial plasma concentration measurements. For QD dosing, planned calculations include AUC0-8h or AUC0-6h and AUC0-24h. For BID dosing, planned calculations include AUC0-8h or AUC0-6h after the morning dose.
Measured: Cycle 1 Days 1-3 and Cycle 2 Day 1, based on protocol-specified serial PK sampling.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2024
- Study start8 Apr 2025
- Primary completionJan 2028 (estimated)
- Study completionJul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CLL / SLLStudies 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
- Randomised
- Intervention model
- Sequential
- Model description
- Part 1 is a non-randomized sequential 3+3 dose-escalation study. Part 2 begins after dose selection and randomizes participants in parallel between two selected lonitoclax dose levels.
- Masking
- None (open label)
- Enrolment
- 84 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
- NCT06708897
- Sponsor's protocol ID
- ZE50-0134-0002
- Status last verified
- Jul 2026
- First submitted
- 22 Nov 2024
- Last updated
- 31 Jul 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of Lonitoclax (ZE50-0134) in Relapsed and Refractory Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL), and Select Low-grade Lymphomas
- ClinicalTrials.gov ID
- NCT06708897
- Acronym / sponsor ID
- ZE50-0134-0002
- Conditions
- CLL / SLL, CLL (Chronic Lymphocytic Leukemia), SLL (Small Lymphocytic Lymphoma), Marginal Zone Lymphoma(MZL), Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia
- Keywords
- Lonitoclax, ZE50-0134, BCL2 inhibitor, relapsed or refractory, dose escalation, dose expansion, dose optimization, BTK inhibitor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 84 participants (estimated)
- Lead sponsor
- Lomond Therapeutics Holdings, Inc.Industry (pharma, biotech, devices)
- Study start
- 8 Apr 2025 (actual)
- Primary completion
- Jan 2028 (estimated)
- Study completion
- Jul 2028 (estimated)
- First posted
- 27 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This Phase 1, open-label, multicenter study is evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of lonitoclax (ZE50-0134) in adults with relapsed or refractory chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and select low-grade B-cell lymphomas.
The study has two sequential parts. Part 1 uses dose escalation to determine the biologically effective dose and/or maximum tolerated dose of lonitoclax. Participants receive a 3-day step-up regimen followed by continuous once-daily or twice-daily oral dosing in 28-day cycles. Part 2 is a randomized dose-expansion comparison of two selected lonitoclax dose levels in venetoclax-naive participants with relapsed or refractory CLL/SLL. Treatment may continue for up to 12 cycles and, for participants deriving clinical benefit, for up to 24 cycles with approval from the Medical Monitor.
Detailed description
This is an open-label, multicenter Phase 1 study with two sequential parts.
Part 1 is a non-randomized dose-escalation study in participants with relapsed or refractory CLL/SLL or select low-grade lymphomas. A standard 3+3 design is used to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of lonitoclax (ZE50-0134), and to identify a biologically effective dose and/or maximum tolerated dose. Planned dose levels include once-daily and twice-daily regimens. Dose Levels 6a and 6b may enroll concurrently. Dose-limiting toxicities are evaluated during Cycle 1.
To reduce the risk of tumor lysis syndrome, participants receive intravenous hydration beginning on Day -1 and a 3-day step-up dosing regimen as inpatients. After step-up dosing, the assigned lonitoclax dose is administered orally once daily or twice daily in a fed state. Each treatment cycle is 28 days.
Part 2 is a randomized dose-expansion portion in venetoclax-naive participants with relapsed or refractory CLL/SLL. Approximately 15 participants are assigned to each of two selected dose levels: the biologically effective dose or maximum tolerated dose and one lower dose level, provided activity is observed. Part 2 evaluates safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity to support selection of a recommended Phase 2 dose.
Treatment is continuous for up to 12 cycles. Participants deriving clinical benefit may continue treatment for up to 24 cycles at the investigator's discretion with Medical Monitor approval. Participants are followed for safety after treatment and for disease progression, subsequent treatment, and survival.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 12
- Model description
- Part 1 is a non-randomized sequential 3+3 dose-escalation study. Part 2 begins after dose selection and randomizes participants in parallel between two selected lonitoclax dose levels.
| Arm | Type | Receives |
|---|---|---|
| Part 1: Dose Level -1 - 75 mg QD | Experimental | Drug: Lonitoclax (ZE50-0134)Optional de-escalation cohort. Participants receive lonitoclax 25 mg once daily on Day 1, 50 mg once daily on Day 2, and 75 mg once daily on Day 3 and thereafter. Treatment is administered orally in a fed state in 28-day cycles. |
| Part 1: Dose Level 1 - 100 mg QD | Experimental | Drug: Lonitoclax (ZE50-0134)Participants receive lonitoclax 25 mg once daily on Day 1, 50 mg once daily on Day 2, and 100 mg once daily on Day 3 and thereafter. Treatment is administered orally in a fed state in 28-day cycles. |
| Part 1: Dose Level 2 - 200 mg QD | Experimental | Drug: Lonitoclax (ZE50-0134)Participants receive lonitoclax 50 mg once daily on Day 1, 100 mg once daily on Day 2, and 200 mg once daily on Day 3 and thereafter. Treatment is administered orally in a fed state in 28-day cycles. |
| Part 1: Dose Level 3 - 400 mg QD | Experimental | Drug: Lonitoclax (ZE50-0134)Participants receive lonitoclax 50 mg once daily on Day 1, 100 mg once daily on Day 2, and 400 mg once daily on Day 3 and thereafter. Treatment is administered orally in a fed state in 28-day cycles. |
| Part 1: Dose Level 4 - 600 mg QD | Experimental | Drug: Lonitoclax (ZE50-0134)Participants receive lonitoclax 50 mg once daily on Day 1, 100 mg once daily on Day 2, and 600 mg once daily on Day 3 and thereafter. Treatment is administered orally in a fed state in 28-day cycles. |
| Part 1: Dose Level 5 - 800 mg QD | Experimental | Drug: Lonitoclax (ZE50-0134)Participants receive lonitoclax 50 mg once daily on Day 1, 100 mg once daily on Day 2, and 800 mg once daily on Day 3 and thereafter. Treatment is administered orally in a fed state in 28-day cycles. |
| Part 1: Dose Level 6a - 1000 mg QD | Experimental | Drug: Lonitoclax (ZE50-0134)Participants receive lonitoclax 100 mg once daily on Day 1, 250 mg once daily on Day 2, and 1000 mg once daily on Day 3 and thereafter. Treatment is administered orally in a fed state in 28-day cycles. Dose Levels 6a and 6b may enroll concurrently. |
| Part 1: Dose Level 6b - 500 mg BID | Experimental | Drug: Lonitoclax (ZE50-0134)Participants receive lonitoclax 50 mg twice daily on Day 1, 100 mg twice daily on Day 2, and 500 mg twice daily on Day 3 and thereafter. Treatment is administered orally in a fed state in 28-day cycles. Dose Levels 6a and 6b may enroll concurrently. |
| Part 1: Dose Level 7b - 750 mg BID | Experimental | Drug: Lonitoclax (ZE50-0134)Participants receive lonitoclax 100 mg twice daily on Day 1, 250 mg twice daily on Day 2, and 750 mg twice daily on Day 3 and thereafter. Treatment is administered orally in a fed state in 28-day cycles. |
| Part 1: Dose Level 8b - 1000 mg BID | Experimental | Drug: Lonitoclax (ZE50-0134)Participants receive lonitoclax 100 mg twice daily on Day 1, 250 mg twice daily on Day 2, and 1000 mg twice daily on Day 3 and thereafter. Treatment is administered orally in a fed state in 28-day cycles. |
| Part 2: Selected Dose A - BED/MTD | Experimental | Drug: Lonitoclax (ZE50-0134)Participants with relapsed or refractory CLL/SLL who are venetoclax naive are randomized to a selected lonitoclax dose corresponding to the biologically effective dose or maximum tolerated dose identified in Part 1. The selected regimen may be once daily or twice daily. Approximately 15 participants are planned. |
| Part 2: Selected Dose B - One Dose Level Lower | Experimental | Drug: Lonitoclax (ZE50-0134)Participants with relapsed or refractory CLL/SLL who are venetoclax naive are randomized to one lonitoclax dose level below the biologically effective dose or maximum tolerated dose selected in Part 1, provided activity is observed. The selected regimen may be once daily or twice daily. Approximately 15 participants are planned. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Men and women aged 18 years or older.
- Disease as defined below:
- Disease requiring therapy in the investigator's opinion.
- Adequate bone marrow, liver, and renal function during screening:
- Eastern Cooperative Oncology Group performance status of 0, 1, or 2.
Key exclusion criteria (16 listed)
- Part 2 only: Prior venetoclax treatment.
- Known active Richter transformation. Participants previously treated for Richter transformation may be eligible if they have been in remission for more than 2 years, have no evidence of Richter transformation, and have CLL only.
- Known hypersensitivity to lonitoclax, its excipients, or an agent administered in association with the study.
- Clinically significant cardiac disease, including congestive heart failure greater than New York Heart Association Class II; uncontrolled coronary artery disease; unstable angina; new-onset angina or myocardial infarction within 6 months before first dose; major regional wall-motion abnormalities on baseline echocardiography; or cardiac arrhythmias requiring antiarrhythmic treatment other than beta-blockers or digoxin.
- Known active cytomegalovirus, hepatitis B virus, or hepatitis C virus infection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lonitoclax (ZE50-0134)Lonitoclax is supplied as immediate-release white opaque soft gelatin capsules in 25 mg, 100 mg, and 250 mg strengths. Participants receive a 3-day step-up regimen followed by the assigned oral dose once daily (QD) or twice daily (BID) in a fed state, administered within 1 hour of food. Each cycle is 28 days. Treatment continues for up to 12 cycles and may continue for up to 24 cycles in participants deriving clinical benefit, at the investigator's discretion with Medical Monitor approval. Participants receive inpatient monitoring and tumor lysis syndrome prophylaxis during the initial step-up period. | Drug | Part 1: Dose Level -1 - 75 mg QD, Part 1: Dose Level 1 - 100 mg QD, Part 1: Dose Level 2 - 200 mg QD, Part 1: Dose Level 3 - 400 mg QD, Part 1: Dose Level 4 - 600 mg QD, Part 1: Dose Level 5 - 800 mg QD, Part 1: Dose Level 6a - 1000 mg QD, Part 1: Dose Level 6b - 500 mg BID, Part 1: Dose Level 7b - 750 mg BID, Part 1: Dose Level 8b - 1000 mg BID, Part 2: Selected Dose A - BED/MTD, Part 2: Selected Dose B - One Dose Level Lower |
Primary outcome
Incidence and severity of treatment-emergent adverse events and serious adverse events
Time frame: From first dose through 30 days after the last dose; treatment may continue for up to 24 cycles (28 days per cycle).
Number and percentage of participants with treatment-emergent adverse events, serious adverse events, clinically significant laboratory abnormalities, adverse events related to lonitoclax, and adverse events leading to treatment discontinuation. Adverse events are graded using NCI CTCAE Version 5.0.
Incidence of dose-limiting toxicities in Part 1
Time frame: Cycle 1 (Days 1-28).
Number and percentage of Part 1 participants experiencing a protocol-defined dose-limiting toxicity during the dose-limiting toxicity assessment period.
Determination of the biologically effective dose and/or maximum tolerated dose
Time frame: After completion of Cycle 1 for evaluable participants in each Part 1 dose cohort.
The selected dose is determined from the totality of safety, dose-limiting toxicity, pharmacokinetic, pharmacodynamic, and early response data across Part 1 dose cohorts according to the protocol-defined dose-escalation rules.
6 secondary outcomes
Overall Response Rate (ORR)
Time frame: From first dose through end of treatment, up to 24 cycles (28 days per cycle).
Duration of response (DOR)
Time frame: From first documented response until progression, death, withdrawal, loss to follow-up, or sponsor termination; assessed during treatment and long-term follow-up.
Progression-free survival (PFS)
Time frame: From first dose until progression, death, withdrawal, loss to follow-up, or sponsor termination; assessed during treatment and long-term follow-up.
Time to next treatment (TTNT)
Time frame: From first dose until initiation of new anticancer treatment, death, withdrawal, loss to follow-up, or sponsor termination.
Maximum observed plasma concentration (Cmax) of lonitoclax
Time frame: Cycle 1 Days 1-4, 8, 15, and 22; Cycle 2 Days 1-2; and end-of-treatment/early-termination sampling as applicable.
Area under the plasma concentration-time curve (AUC) of lonitoclax
Time frame: Cycle 1 Days 1-3 and Cycle 2 Day 1, based on protocol-specified serial PK sampling.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lonitoclax (ZE50-0134) in people with CLL / SLL and CLL (Chronic Lymphocytic Leukemia), run by Lomond Therapeutics Holdings, Inc. at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 31 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ekaterina Dokukina, PhD MD (+1 858 353 4108, kdokukina@eileanther.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and severity of treatment-emergent adverse events and serious adverse events (time frame: From first dose through 30 days after the last dose; treatment may continue for up to 24 cycles (28 days per cycle).). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2026.