APG-2575 for CLL
Recruiting in Palo Alto (17 mi)
+8 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Ascentage Pharma Group Inc.
Must not be taking: CYP3A inhibitors, CYP3A inducers
Disqualifiers: HIV, Hepatitis B, CNS involvement, others
No Placebo Group
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?
Assess the safety and tolerability, identify dose-limiting toxicities (DLT) and determine the maximum tolerated dose (MTD) / recommended phase 2 dose (RP2D) of APG-2575.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, you cannot take certain medications like strong CYP3A inhibitors or inducers within 7 days before starting the trial.
What data supports the effectiveness of the drug APG-2575 (Lisaftoclax) for treating chronic lymphocytic leukemia (CLL)?
Venetoclax, a drug similar to APG-2575, has shown effectiveness in treating CLL, especially in patients with high-risk features, by achieving significant remission rates and being generally well-tolerated. This suggests that APG-2575, which may work in a similar way, could also be effective for CLL.12345
Eligibility Criteria
This trial is for adults over 18 with chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) who have tried at least one treatment without success and need more therapy. They should be relatively active (ECOG ≤2), show signs of disease progression, and meet specific blood count and organ function criteria.Inclusion Criteria
I can take care of myself and am up and about more than 50% of my waking hours.
My platelet count is high enough without needing a transfusion in the past week.
Females of childbearing potential and non-sterile males must practice at least one of the following methods of birth control with partner(s) throughout the study and for 90 days after discontinuing study drug: Total abstinence from sexual intercourse, Surgically sterile partner(s), Intrauterine device (IUD), Double-barrier method, Hormonal contraceptives for at least 3 months prior to study drug administration, Male patients must refrain from sperm donation from initial study drug administration until 90 days after the last dose of study drug, Ability to understand and willingness to sign a written informed consent form, Willingness and ability to comply with study procedures and follow-up examination
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Exclusion Criteria
Any other condition or circumstance that would make the patient unsuitable for participation in the study
I have not had radiation therapy in the last 14 days.
I have an active hepatitis B or C infection.
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Ramp-up
Participants undergo a ramp-up period with APG-2575 starting at 20 mg and increasing to a maximum of 1200 mg over several days
3-9 days
Dose Escalation and Expansion
APG-2575 is studied at different dose levels as monotherapy and in combination with other agents using a 3+3 dose escalation design, followed by dose expansion at RP2D
6 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Treatment Details
Interventions
- APG2575 (Bcl-2 inhibitor)
Trial OverviewThe study tests APG-2575 alone or with other treatments to find the safest dose that's still effective for CLL/SLL. It aims to identify any toxic effects at different doses and establish a recommended dosage for future phase 2 trials.
Participant Groups
6Treatment groups
Experimental Treatment
Group I: APG2575 800mgExperimental Treatment1 Intervention
APG2575 800mg ramp up
Group II: APG2575 400mgExperimental Treatment1 Intervention
APG2575 400mg ramp up
Group III: APG2575 200mgExperimental Treatment1 Intervention
APG2575 200mg ramp up
Group IV: APG2575 1200mgExperimental Treatment1 Intervention
APG2575 1200mg ramp up
Group V: APG2575 1000 mgExperimental Treatment1 Intervention
APG2575 1000 mg ramp up
Group VI: APG 2575 600mgExperimental Treatment1 Intervention
APG2575 600mg ramp up
APG2575 is already approved in China for the following indications:
🇨🇳 Approved in China as Lisaftoclax for:
- Relapsed/refractory chronic lymphocytic leukemia (CLL)
- Small lymphocytic lymphoma (SLL)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Gabrail Cancer CenterCanton, OH
Dana Farber Cancer InstituteBoston, MA
Swedish HealthSeattle, WA
Mayo ClinicJacksonville, FL
More Trial Locations
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Who Is Running the Clinical Trial?
Ascentage Pharma Group Inc.Lead Sponsor
References
Molecular Remission Using Low-Dose Immunotherapy with Minimal Toxicities for Poor Prognosis IGHV- Unmutated Chronic Lymphocytic Leukemia. [2021]Chronic lymphocytic leukemia (CLL) accounts for 10% of hematologic malignancies. CLL is a malignancy of CD5+ B cells and it is characterized by the accumulation of small, mature-appearing neoplastic lymphocytes in the blood, bone marrow, and secondary lymphoid tissues. In the present case, a middle-aged female patient with poor prognosis unmutated IGHV CLL achieved cytogenetic and molecular remission with minimal adverse events following six cycles of low dose recombinant human IL-2 (rIL-2) in combination with low dose targeted venetoclax. Personalized low dose rIL-2 in combination with either lenalidomide or venetoclax mediates natural killer stimulation and is an effective non-toxic immunotherapy administered in the outpatient setting for poor prognosis CLL.
Current strategies to create tailored and risk-adapted therapies for CLL patients. [2021]Given the current dynamics in the development of novel agents for CLL therapy, the task to find optimal, non-toxic combinations has become the primary goal. This article gives an update of the most interesting novel drugs. The strategy of the German CLL Study Group to use these agents in combinations is described in detail, highlighting the strategy and first results of a recently started series of phase II combination trials, the BXX series using agents such as bendamustine, idelalisib, ibrutinib, obinutuzumab, ofatumumab and venetoclax.
BCL-2 as a therapeutic target in chronic lymphocytic leukemia. [2017]Venetoclax (formerly ABT-199) was recently approved in the United States for the treatment of patients who have relapsed or refractory chronic lymphocytic leukemia (CLL) with the 17p deletion. Venetoclax has demonstrated marked activity as monotherapy as well as in combination with cytotoxic chemotherapies, B-cell receptor inhibitors, and anti-CD20 monoclonal antibodies across the spectrum of CLL. The potency of venetoclax has been associated with a unique ability to induce deep (minimal residual disease-negative) complete remissions that appear to be durable. Its toxicity profile includes manageable hematologic toxicities, as well as the potential for tumor lysis syndrome. Here, we review the BCL-2 pathway and the mechanism of action of BCL-2 inhibitors, the activity and safety profile of venetoclax, and the practical application of venetoclax in the management of patients with CLL.
Venetoclax for patients with chronic lymphocytic leukemia who progressed during or after idelalisib therapy. [2021]B-cell receptor pathway inhibitors (BCRis) have transformed treatment of chronic lymphocytic leukemia (CLL); however, the efficacy of therapies for patients whose disease is refractory to/relapses after (R/R) BCRis is unknown. Venetoclax is a selective, orally bioavailable BCL-2 inhibitor with activity in patients with CLL, including those who are heavily pretreated or have 17p deletion. This phase 2 study prospectively evaluated venetoclax in patients with R/R CLL after ibrutinib or idelalisib; here we report on patients who received idelalisib as the last BCRi before enrollment. Venetoclax was initiated at 20 mg daily, followed by intrapatient ramp-up to 400 mg daily. Primary objectives included efficacy (objective response rate [ORR]) and safety of venetoclax. The study enrolled 36 patients who previously received idelalisib (ORR, 67% [24/36]); 2 patients achieved complete remission, and 1 had complete remission with incomplete bone marrow recovery. Median progression-free survival (PFS) has not yet been reached; estimated 12-month PFS was 79%. The most common adverse events (AEs; all grades) were neutropenia (56%), diarrhea (42%), upper respiratory tract infection (39%), thrombocytopenia (36%), nausea (31%), fatigue (28%), cough (22%), rash (22%), and anemia (22%). Grade 3 or 4 AEs were primarily hematologic (neutropenia [50%], thrombocytopenia [25%], and anemia [17%]). No patients experienced tumor lysis syndrome. Venetoclax demonstrated promising clinical activity and favorable tolerability in patients with CLL whose disease progressed during or after idelalisib therapy. This trial was registered at www.clinicaltrials.gov as #NCT02141282.
Comprehensive Safety Analysis of Venetoclax Monotherapy for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia. [2019]Purpose: The oral BCL-2 inhibitor venetoclax is an effective therapy for patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), including disease with high-risk genomic features such as chromosome 17p deletion [del(17p)] or progressive disease following B-cell receptor pathway inhibitors.Patients and Methods: We conducted a comprehensive analysis of the safety of 400 mg daily venetoclax monotherapy in 350 patients with CLL using an integrated dataset from three phase I/II studies.Results: Median age was 66 years and 60% had del(17p). Patients had received a median of three prior therapies (range: 0-15); 42% previously received ibrutinib or idelalisib. Median duration of exposure to venetoclax was 16 months (0-56). In the pooled analysis, the most common adverse events (AE) of any grade were diarrhea (41%), neutropenia (40%), nausea (39%), anemia (31%), fatigue (28%), and upper respiratory tract infection (25%). The most common grade 3/4 AEs were neutropenia (37%), anemia (17%), and thrombocytopenia (14%). With the current 5-week ramp-up dosing, the incidence of laboratory TLS was 1.4% (2/166), none had clinical sequelae, and all of these patients were able to ramp-up to a daily dose of 400 mg. Grade 3/4 neutropenia was manageable with growth factor support and dose adjustments; the incidence of serious infections in these patients was 15%. Ten percent of patients discontinued venetoclax due to AEs and 8% died while on study, with the majority of deaths in the setting of disease progression.Conclusions: Venetoclax as a long-term continuous therapy is generally well tolerated in patients with R/R CLL when initiated with the current treatment algorithm. Clin Cancer Res; 24(18); 4371-9. ©2018 AACR.