A Phase 1 Study of ZE50-0134 in Relapsed and Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, and Select Low-grad Lymphomas

NCT06708897 | Recruiting Phase 1 FDA Drug

• 1 other identifier: ZE50-0134-0002
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 4

Brief Summary

This is a clinical study aiming to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of ZE50-0134 in relapsed and refractory chronic lymphocytic leukemia, small lymphocytic lymphoma, and select low-grad lymphomas.

Conditions

CLL / SLL; CLL (Chronic Lymphocytic Leukemia); SLL (Small Lymphocytic Lymphoma)

Outcome Measures

Primary Outcomes (1)

• Incidence of AEs and SAEs

  Frequency, severity, and relationship to study drug of any TEAEs or abnormalities of laboratory tests; SAEs; and AEs leading to discontinuation of study treatment

  Up to 24 cycles, 4 weeks each

Secondary Outcomes (5)

• Overall Response Rate (ORR)

  Up to 24 cycles, 4 weeks each

• Assess duration of response (DOR)

  Up to 24 cycles, 4 weeks each

• Progression-free survival (PFS)

  Up to 24 cycles, 4 weeks each

• Time to next treatment (TTNT)

  Up to 24 cycles, 4 weeks each

• ZE50-0134 blood plasma concentration

  2 cycles, 4 weeks each

Other Outcomes (3)

• Caspase 3 activation level

  3 cycles, 4 weeks each

• Immune cells count

  3 cycles, 4 weeks each

• Rate of undetectable Measurable residual disease (uMRD) response in bone marrow and blood

  12 cycles, 4 weeks each

Study Arms (8)

ZE50-0134 Dose Level -1

EXPERIMENTAL

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

Drug: ZE 50-0134

ZE50-0134 Dose Level 1

EXPERIMENTAL

Drug: ZE 50-0134

ZE50-0134 Dose Level 2

EXPERIMENTAL

Drug: ZE 50-0134

ZE50-0134 Dose Level 3

EXPERIMENTAL

Drug: ZE 50-0134

ZE50-0134 Dose Level 4

EXPERIMENTAL

Drug: ZE 50-0134

ZE50-0134 Dose Level 5

EXPERIMENTAL

Drug: ZE 50-0134

ZE50-0134 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: ZE 50-0134

ZE50-0134 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: ZE 50-0134

Interventions

ZE 50-0134 DRUG

oral capsules QD

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

Eligibility Criteria

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

You may qualify if:

• Men and women aged ≥18 years.
• Disease as defined below:
• Part 1: Patients with symptomatic CLL or SLL (defined by iwCLL) without del(17p)/TP53 must have received ≥2 prior therapies that have included a BTKi and venetoclax (or declined this) or Patients with progressive low-grade lymphoma that includes marginal zone lymphoma, lymphoplasmacytic lymphoma (including Waldenstrom's macroglobulinemia) who have received at least 2 therapies including a BTKi and CD20 antibody-based therapy.
• Part 2: Patients with symptomatic CLL or SLL (defined by iwCLL) must have received ≥1 prior therapies that have included a BTKi and be venetoclax naive.
• Prior to beginning part 2, an activation amendment will be submitted to the FDA that includes safety, pharmacokinetics, pharmacodynamics and early efficacy data from the Part 1 portion. At this time, we may also include cohorts of specific types of low-grade lymphoma as well. Adequate bone marrow, liver, and renal functions as assessed by the following laboratory requirements to be conducted within 7 days before the first dose of study drug:
• Absolute neutrophil count (ANC) \> 0.75 x 109/L. For subjects with documented bone marrow involvement ≥ 0.5 x 109/L
• Platelet count \> 50 x 109/L. For subjects with documented bone marrow involvement ≥ 30 x 109/L
• Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≤ 3.0 x upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 x ULN
• Creatinine or Cystatin C glomerular filtration rate (GFR) ≥60 mL/min. Estimated GFR (eGFR) according to the Modification of Diet in Renal Disease Study Group (MDRD) formula and expressed in mL/min. To convert mL/min/1.73 m2 to mL/min multiply by the individual's BSA calculated using an appropriate formula and divide by 1.73 Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less Negative serum or urine pregnancy test must be obtained within 7 days before the first dose of study drug in women of childbearing potential. Negative results must also be available before each cycle.
• Postmenopausal women, as defined below, are exempt from pregnancy testing:
• Age \>50 years with amenorrhea for at least 12 months or
• Age ≤50 years with 6 months of spontaneous amenorrhea and follicle stimulating hormone (FSH) level within postmenopausal range (\>40 mIU/mL) OR
• Permanently sterilized women (e.g., hysterectomy, bilateral salpingectomy, or uterine ablation) Women and men of reproductive potential must agree to use highly effective contraception when sexually active. This applies for the period between signing of the informed consent and 90 days after the last administration of study drug. These methods should be documented in source documents. The investigator or a designated associate is requested to advise the subject on how to achieve highly effective birth control. Ability to understand and the willingness to sign a written informed consent. A signed informed consent (including consent for genetic biomarker

You may not qualify if:

• Subjects will be excluded from the study if they display any of the following criteria:
• FOR PART 2 ONLY
• \- No prior venetoclax treatment
• FOR BOTH PARTS ALL THE FOLLOWING APPLY:
• Know active Richter's transformation. Patients who have been treated for this diagnosis and have been in remission for \> 2 years without evidence of this and who have only CLL are considered eligible
• Known hypersensitivity to the study drug or excipients of the preparation or any agent given in association with this study.
• Clinically significant cardiac disease including congestive heart failure \> New York Heart Association (NYHA) Class II, evidence for uncontrolled coronary artery disease (e.g., unstable angina (anginal symptoms at rest) or new-onset angina (within the last 6 months or myocardial infarction within the past 6 months before first dose, major regional wall motion abnormalities upon baseline echocardiography), and cardiac arrhythmias requiring anti- arrhythmic therapy except for beta-blockers and digoxin.
• Known Active cytomegalovirus (CMV), hepatitis B or C virus infection.
• Known Active SARS-CoV-2 infection; prior SARS-CoV-2 infection allowed if completely recovered \> 14 days.
• Active clinically serious infections of Grade \>2, requiring parenteral therapy; Subjects may be eligible after infection resolves.
• Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura within 28 days of enrolment.
• Allogeneic bone marrow transplant within 4 months before first dose of study drug (Subjects must have completed immunosuppressive therapy before enrollment).
• A physical exam or laboratory finding that contraindicates the use of investigational therapy or otherwise places the subject at excessively high risk for treatment, as determined by the investigator. A discussion between the investigator and sponsor regarding eligibility is encouraged for such cases.
• Unresolved toxicity of previous treatments (excluding cases of alopecia) Grade ≥2.
• Requires ongoing immunosuppressive therapy, including systemic (e.g., intravenous or oral) corticosteroids for the treatment of cancer or other conditions. Note: Subjects may use topical or inhaled corticosteroids or low-dose steroids (≤10 mg of prednisone or equivalent per day) as therapy for comorbid conditions. Short courses of steroids before first dose are allowed for tumor flare.

Sponsors & Collaborators

• Lomond Therapeutics Holdings, Inc.: lead

Study Sites (4)

Norton Cancer Institute, St. Matthews Campus

Louisville, Kentucky, 40207, United States

RECRUITING

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

RECRUITING

University of Cincinnati

Cincinnati, Ohio, 45221, United States

RECRUITING

The Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Ekaterina Dokukina, PhD MD

CONTACT

+38269728309; kdokukina@eileanther.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: November 22, 2024
• First Posted: November 27, 2024
• Study Start: April 8, 2025
• Primary Completion: March 1, 2026
• Study Completion (Estimated): April 1, 2028
• Last Updated: December 5, 2025

Record last verified: 2025-11

Locations

US (4)