ClinicalTrials.gov record NCT06708897
A Study of Lonitoclax (ZE50-0134) in Relapsed or Refractory B-cell Malignancies
Phase 1 Study of Lonitoclax (ZE50-0134) in Relapsed and Refractory Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL), and Select Low-grade Lymphomas
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
This is an open-label Phase 1 study testing lonitoclax in people with relapsed or refractory CLL/SLL and select low-grade B‑cell lymphomas. Part 1 uses dose escalation with a 3-day inpatient step-up and oral once- or twice-daily dosing to find an appropriate dose. Part 2 randomizes venetoclax‑naive CLL/SLL participants between two selected dose levels to further evaluate safety and activity; treatment is given in 28-day cycles for up to 12 cycles (possible extension to 24 cycles with approval).
What it is studying. The study aims to learn what doses of lonitoclax are safe and tolerable, how the drug behaves in the body (pharmacokinetics and pharmacodynamics), and whether there is early evidence of anti-tumor activity in relapsed or refractory B‑cell cancers.
What the researchers hope to learn. To define safe and tolerable dose(s) of lonitoclax, characterize its pharmacokinetics and pharmacodynamics, assess treatment-emergent adverse events and dose-limiting toxicities, and gather preliminary data on anti-tumor activity to support selection of a recommended Phase 2 dose.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
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.
Interventions being studied
Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.
- Drug
- Lonitoclax (ZE50-0134)
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
Inclusion criteria
- 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:
- 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.
Exclusion criteria
- 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.
- 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.
Study description and what participation involves
The study's detailed description, as published on ClinicalTrials.gov.
Show the detailed description from the registry
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.
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
If you join, you will have an initial inpatient period for a 3‑day step‑up dosing of the study drug with intravenous hydration and close monitoring to reduce the risk of tumor lysis syndrome. After the step‑up, you will take oral lonitoclax once or twice daily with food in 28‑day treatment cycles. During treatment you will have clinic visits for safety checks and blood sampling for drug levels and other lab tests, and you will be asked to agree to genetic biomarker testing of tissue and plasma. Treatment may continue for up to 12 cycles and, if you and the study team agree you are deriving clinical benefit and the Medical Monitor approves, for up to 24 cycles; you will be followed after treatment for safety, disease progression, subsequent therapies, and survival.
How the study is structured. Open-label Phase 1 interventional study with two sequential parts. Part 1 is a non-randomized dose-escalation (3+3) phase with a 3-day inpatient step-up dosing period and tumor lysis syndrome prophylaxis, followed by continuous oral dosing in 28-day cycles to identify a biologically effective dose and/or maximum tolerated dose. Part 2 is a randomized dose-expansion in venetoclax‑naive relapsed/refractory CLL/SLL, comparing two dose levels identified from Part 1 (about 15 participants per dose). There is no masking; participants are followed for safety, disease progression, subsequent treatment, and survival.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- This is an early-phase study, mainly about safety and dose. What is already known about this treatment?
- The listed sites are in United States. Is any of them reachable for me, and does the study help with travel?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on Waldenström macroglobulinemia
Important dates
- Study start
- Apr 8, 2025
- Primary completion
- January 2028 (estimated)
- Study completion
- July 2028 (estimated)
- Target enrollment
- 84 participants (estimated)
- Last updated on registry
- Jul 31, 2026
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- Lomond Therapeutics Holdings, Inc.
Central study contact
If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.
- Ekaterina Dokukina, PhD MD 📞 +1 858 353 4108 ✉ kdokukina@eileanther.com
Participating sites (5)
- Norton Cancer Institute, St. Matthews CampusRecruiting
Louisville, Kentucky, 40207 · United States
- University of North Carolina at Chapel HillRecruiting
Chapel Hill, North Carolina, 27599 · United States
- University of CincinnatiRecruiting
Cincinnati, Ohio, 45221 · United States
- The Ohio State UniversityRecruiting
Columbus, Ohio, 43210 · United States
- UT Southwestern Medical CenterNot Yet Recruiting
Dallas, Texas, 75390 · United States
Terms used on this page · explanations by MedicalUpdates.ai
- open-label
- No masking is used, so the assigned intervention is not deliberately hidden from participants or study staff.
- pharmacokinetics
- How the body absorbs, distributes, breaks down and removes a drug. It is studied by measuring drug levels or related substances at set times after a dose.
- pharmacodynamics
- What a drug does to the body, for example how it changes a blood marker or a symptom, and how that relates to the dose.
- relapsed or refractory
- A condition that has not responded to a treatment. 'Relapsed' means it responded and then came back; 'refractory' means it did not respond in the first place.
- dose escalation
- Groups of participants receive increasing doses of a treatment, one group after another, to find a dose that can be given safely.
- maximum tolerated dose
- The highest dose found in a dose-escalation study that can be given without too many dose-limiting side effects.
- randomized
- Participants are assigned to the study groups by chance, like a coin toss, rather than chosen by the doctor or the participant. This is done so the groups are comparable.
- prior therapy
- Treatment a person has already had for the condition. A 'line of therapy' is one course of treatment; studies often require, or limit, the number of prior lines.
- during screening
- The checks done before enrolment to see whether a person qualifies, such as tests, scans or a review of medical history.
- Absolute neutrophil count
- The number of neutrophils, a type of white blood cell that fights infection, in a blood sample. Studies often require it to be above a set level.
- upper limit of normal
- The highest value of a blood test that a laboratory considers normal. Criteria such as '≤ 3 × ULN' mean the result must be no more than three times that value.
- glomerular filtration rate
- A blood-test estimate of how well the kidneys are filtering. Lower numbers mean reduced kidney function; many studies set a minimum value.
- performance status
- A scale from 0 to 5 that describes how a person's condition affects daily activity. 0 means fully active; 1 means restricted in strenuous activity; 2 means able to self-care but unable to work; higher numbers mean more limitation.
- women of childbearing potential
- Studies often ask participants who could become pregnant, or could father a child, to use contraception during the study and for a period afterwards, because the effect of the treatment on a pregnancy is unknown.
- informed consent
- The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
- study drug
- A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
- biomarker
- Something measurable in the body, such as a blood test result or an imaging finding, that indicates how a condition or treatment is behaving.
- baseline
- Measurements taken at the start of the study, before any study treatment, so that later results can be compared with them.
- echocardiography
- An ultrasound scan of the heart. A transesophageal echocardiogram is done through a probe passed into the food pipe for a closer view.
- enrollment
- The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
- bone marrow transplant
- A procedure that replaces blood-forming cells after high-dose treatment. 'Autologous' uses the person's own cells collected beforehand; 'allogeneic' uses cells from a donor.
- Immunosuppressive
- A medicine that reduces the activity of the immune system. Studies of autoimmune conditions often require a stable dose, a prior failure, or a washout of such medicines.
- corticosteroids
- Steroid medicines, such as prednisone, that reduce inflammation. Studies often require a stable dose at entry or measure whether the study treatment allows the dose to be reduced.
- Inclusion Criteria
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- Exclusion Criteria
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
- Dose-limiting toxicities
- A side effect, defined in advance, that is severe enough to limit how far the dose can be raised in a dose-escalation study. How many such events stop escalation is set by the study's rules.
- recommended Phase 2 dose
- The dose chosen at the end of a phase 1 study for testing in later studies, based on safety and other measurements.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this website; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
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