A Study of Lonitoclax (ZE50-0134) in Relapsed or Refractory B-cell Malignancies

Part of paid clinical trials in Louisville, Kentucky.

Sponsor
Lomond Therapeutics Holdings, Inc.
Study ID
NCT06708897
Phase
PHASE1
Status
Recruiting
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Conditions

  • CLL (Chronic Lymphocytic Leukemia)
  • CLL / SLL
  • Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia
  • Marginal Zone Lymphoma(MZL)
  • SLL (Small Lymphocytic Lymphoma)

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • 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 Details

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.

Key Dates

First listed
Nov 27, 2024
Start date
Apr 8, 2025
Status verified
Jul 2026
Primary completion
Jan 31, 2028
Completion
Jul 31, 2028

Study Design

Enrollment
84 participants (estimated)
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Part 1: Dose Level 6a - 1000 mg QD
    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.
  • Experimental: Part 1: Dose Level 6b - 500 mg BID
    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.
  • Experimental: Part 1: Dose Level 7b - 750 mg BID
    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.
  • Experimental: Part 1: Dose Level 8b - 1000 mg BID
    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.
  • Experimental: Part 2: Selected Dose A - BED/MTD
    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.
  • Experimental: Part 2: Selected Dose B - One Dose Level Lower
    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.
  • Experimental: Part 1: Dose Level -1 - 75 mg QD
    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.
  • Experimental: Part 1: Dose Level 1 - 100 mg QD
    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.
  • Experimental: Part 1: Dose Level 2 - 200 mg QD
    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.
  • Experimental: Part 1: Dose Level 3 - 400 mg QD
    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.
  • Experimental: Part 1: Dose Level 4 - 600 mg QD
    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.
  • Experimental: Part 1: Dose Level 5 - 800 mg QD
    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.

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). ]

Central Contacts

Locations (5)

FacilityCityStateZIPSite coordinators
Norton Cancer Institute, St. Matthews CampusLouisvilleKentucky40207-
University of North Carolina at Chapel HillChapel HillNorth Carolina27599-
University of CincinnatiCincinnatiOhio45221-
The Ohio State UniversityColumbusOhio43210-
UT Southwestern Medical CenterDallasTexas75390-

Find similar trials in Louisville, KY

By research site
Norton Cancer Institute, St. Matthews Campus· Louisville, KYUniversity of North Carolina at Chapel Hill· Chapel Hill, NCUniversity of Cincinnati· Cincinnati, OHThe Ohio State University· Columbus, OHUT Southwestern Medical Center· Dallas, TX

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