Safety, tolerability, and pharmacokinetics of lisaftoclax (APG-2575)-based therapy in patients with chronic lymphocytic leukemia: Phase 1b/2 study.
Matthew S Davids, Asher Chanan-Khan, Sikander Ailawadhi...
https://pubmed.ncbi.nlm.nih.gov/41109219Actively Recruiting
Phase 1
Age: 18Years - 85Years
All Genders
ID04215809
APG-2575CU101, A Phase Ib Study of APG-2575 as a Single Agent or in Combination With Other Therapeutic Agents in Patients With Relapsed and/or Refractory Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
Led by Ascentage Pharma Group Inc. · Updated on 2025-04-10
144
Participants Needed
9
Research Sites
86 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating lisaftoclax, a drug being studied alone or combined with other therapies, for patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The main goals are to assess the safety, tolerability, identify dose-limiting toxicities (DLT), and determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of lisaftoclax. This research focuses on patients who need treatment after prior therapies and aims to better understand the dosing and safety profile of this drug. The trial is conducted in two parts, each including a ramp-up period, dose escalation, and dose expansion phases. The ramp-up involves gradually increasing doses of lisaftoclax from 20 mg to up to 1,000 mg daily over several days, depending on the assigned dose level. Part 1 studies lisaftoclax alone at various doses (400 mg, 600 mg, 800 mg, and 1,000 mg), while Part 2 evaluates lisaftoclax combined with rituximab or acalabrutinib through a dose escalation and expansion design to further assess safety and anticancer activity. Participants will be closely monitored with assessments including safety evaluations and toxicity checks over a 42-day period to identify dose-limiting toxicities and maximum tolerated dose. The study requires patients to attend visits for treatment administration, follow-up examinations, and to provide informed consent. Researchers will track outcomes related to safety and dosing to inform future studies. The trial is designed for adults aged 18 to 85 with relapsed or refractory CLL/SLL, and participants will be followed throughout the study duration as per protocol.
CONDITIONS
Brief Title
Study of APG-2575 as a Single Agent or in Combination With Other Therapeutic Agents for CLL/SLL
Who Can Participate
Age: 18Years - 85Years
All Genders
Eligibility Criteria
You may qualify if you...
- 18 years of age or older
- Histologically confirmed chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) with relapse or refractory to at least one prior therapy
- Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
- Documented disease progression prior to study entry with symptoms like increasing lymphocyte count, enlarging lymph nodes or spleen, increasing cytopenias, or clinical B symptoms
- Adequate bone marrow function independent of growth factors
- Adequate kidney and liver function as defined by specified lab values
- Negative pregnancy test for females of childbearing potential before dosing
- Use of effective birth control methods for females of childbearing potential and non-sterile males during and 90 days after study
- Male patients must avoid sperm donation during and 90 days after treatment
- Ability to understand and sign informed consent
- Willingness and ability to comply with study procedures and follow-up
You will not qualify if you...
- Allogeneic stem cell transplant within 90 days
- Active graft-versus-host disease or immunosuppressive therapy
- CAR-T cell therapy within 30 days
- Richter's Syndrome unless in remission
- Prior anti-BCL-2 treatment except in specified cases
- Discontinuation due to acalabrutinib toxicity or use of proton pump inhibitors at study entry for combination cohort
- Anticoagulation therapy with warfarin or equivalent within 7 days of first dose
- Active infections including HIV, hepatitis B or C, or COVID-19
- Known central nervous system involvement
- Prior malignancy with recurrence within 2 years except certain skin and cervical/breast cancers
- Recent treatment with other investigational or anticancer therapies within specified timeframes
- Pregnancy or breastfeeding
- Recent use of high-dose steroids or certain CYP3A inhibitors or inducers
- Radiation within 14 days
- Ongoing toxicities from prior treatments not recovered to baseline except alopecia or neuropathy
- Incomplete recovery from major surgery within 28 days
- Significant cardiovascular conditions including NYHA Class 2 or higher, unstable angina, or recent heart attack
- Abnormal ECG findings including prolonged QTc or heart block
- Inability to swallow capsules or gastrointestinal conditions affecting absorption
- Uncontrolled illnesses or psychiatric/social conditions limiting compliance
- Other conditions judged unsuitable by the investigator
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
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Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
Run-in Period
Duration - 3 to 8 days depending on dose level
Participants undergo a ramp-up dosing schedule where lisaftoclax is administered daily in increasing doses until the target dose is reached.
Daily visits for up to 8 days
Treatment
Duration - Up to 42 days per cycle or until disease progression or discontinuation
Participants receive lisaftoclax as monotherapy or in combination with rituximab or acalabrutinib at assigned dose levels to evaluate safety and anticancer activity.
Visits scheduled according to treatment cycles
Trial Site Locations
Total: 9 locations
1
City of Hope
Duarte, California, United States, 91010
Actively Recruiting
2
Mayo Clinic
Jacksonville, Florida, United States, 32224
Actively Recruiting
3
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Actively Recruiting
4
Novant Health
Charlotte, North Carolina, United States, 28204
Actively Recruiting
5
Gabrail Cancer Center
Canton, Ohio, United States, 44718
Actively Recruiting
6
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Actively Recruiting
7
Swedish Health
Seattle, Washington, United States, 98122
Actively Recruiting
8
Princess Alexandria Hospital
Brisbane, Queensland, Australia, QLD 4102
Actively Recruiting
9
Frankston Private Hospital
Melbourne, Victoria, Australia, 3199
Actively Recruiting
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Research Team
L
Laura Glass
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
4
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