- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03913949
A Study to Evaluate the Safety,PK and PD of APG-2575 in Patients With Hematologic Malignancies
January 4, 2024 updated by: Ascentage Pharma Group Inc.
A Phase I Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Properties of Orally Administered APG-2575 in Patients With Hematologic Malignancies
The purpose of this study is to assess the safety, tolerability, pharmacokinetic and pharmacodynamic properties of APG-2575 in patients with relapse or refractory chronic lymphocytic leukemia and non-hodgkin's lymphoma.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
Detailed Description
This is a multi-center, single-agent, open-label, Phase I study of APG-2575.
The study consists of the dose escalation stage and the dose expansion stage.
APG-2575 will be administered orally, once daily for consecutive 4 weeks as one cycle.
Initially, the start dose is 20mg.
Single patient cohorts will be evaluated, the dose of APG-2575 will be increased in subsequent cohorts, to 50 mg, 100 mg, 200 mg, 400 mg, 600mg and 800mg accordingly.
If there is any one of the following event is observed, a dose-limiting toxicity (DLT), two drug related Grade 2 toxicities or one drug related ≥ Grade 3 toxicity, or laboratory or clinical tumor lysis syndrome (TLS), or suspected hypersensitivity reaction occur in Cycle 1, the dose escalation will convert to the standard 3+3 design, If ≥ 2/6 patients develop DLT at any dose level dose escalation will cease and the dose level immediately below will be expanded to 6 patients.
If ≤ 1/6 patients develop a DLT at the highest dose reached this will be declared the MTD.
After the MTD/Recommended Phase II Dose (RP2D) is defined, a maximum of 40 patients will be treated at that dose level.
Study Type
Interventional
Enrollment (Estimated)
74
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Yifan Zhai, MD
- Phone Number: 2405056608
- Email: yzhai@ascentagepharma.com
Study Contact Backup
- Name: ZI CHEN, MD
- Phone Number: +86 18117275173
- Email: yjhuang@ascentagepharma.com
Study Locations
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Anhui
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Hefei, Anhui, China
- Anhui Procincial hospital
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Henan
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Zhengzhou, Henan, China
- Henan Provincial Oncology Hospital
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Hubei
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Wuhan, Hubei, China
- Zhongnan Hospital of Wuhan University
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Tianjin
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Tianjin, Tianjin, China, 300020
- Blood Diseases Hospital Chinese Academy of Medical Sciences
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Zhejiang
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Hangzhou, Zhejiang, China
- The First Affiliated Hospital, Zhejiang University School of Medicin
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Age ≥18 years old.
- Histologically confirmed diagnosis of chronic lymphocytic leukemia, or non-Hodgkin's lymphoma such as mantle cell lymphoma, diffuse large B cell lymphoma, Waldenstrom macroglobulinemia (WM).
- Patient must have relapsed or refractory to, intolerant to, or are considered ineligible for therapies known to provide clinical benefit.
- Life expectancy ≥ 3 months.
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): 0 -1 in dose escalation; 0-2 in dose expansion.
- Corrected QT interval ≤450ms in males, and ≤470ms in females.
Adequate bone marrow function independent of growth factor:
- Absolute neutrophil count (ANC) ≥1.0 X 10E9/L.
- Hemoglobin ≥ 8.0 g/dL.
- Platelets count ≥ 30 X 10E9/L (entry platelet count must be independent of transfusion within 7 days of first dose).
Adequate renal and liver function as indicated by:
- Serum creatinine ≤ 1.5 x upper limit of normal (ULN); if serum creatinine is >1.5 X ULN, creatinine clearance must be ≥60 mL/min.
- Total bilirubin ≤1.5 x ULN, except subject with known Gilbert's syndrome.
- Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) <2.5 x ULN.
- Alkaline phosphatase < 2.5 x ULN and < 5 x for bone metastases &/or no hepatic parenchymal metastases on screening radiographic examination.
- Thromboplastin time (aPTT)≤1.5 X ULN unless the subject is receiving anticoagulant therapy as long as prothrombin time (PT) or aPTT is within therapeutic range of intended use of anticoagulants.
- Willingness by both males, and female patients of child bearing potential, to use contraception by a method that is deemed effective by the investigator, throughout the treatment period and for at least three months following the last dose of study drug Postmenopausal women must be amenorrheal for at least 12 months to be considered of non-childbearing potential. All partners must have the same willingness for contraception methods throughout the treatment period and for at least three months following the last dose of study drug as well.
- Ability to understand and willingness to sign a written informed consent form (the consent form must be signed by the patient prior to any study-specific procedures).
- Willingness and ability to comply with study procedures and follow-up examination.
Exclusion Criteria:
Patients who meet any of the following exclusion criteria are not to be enrolled in this study:
- Prior history of allogeneic cell transplant.
- Subjects have been diagnosed with Burkitt's lymphoma, Burkitt-like lymphoma, or lymphoblastic lymphoma/leukemia.
- Received chemotherapy within 14 days prior to entering the study.
- Received biologic (< 28 days), small molecule targeted therapies (< 5 half-life) or other anti-cancer therapy within 21 days of study entry.
- Concurrent treatment with an investigational agent, 14 days for small molecular agents and/or 28 days for biologics treatment prior to the first dose of therapy.
- Radiation within 14 days of study entry, thoracic radiation within 28 days of study entry.
- Has gastrointestinal conditions that could affect the absorption of APG-2575 in the opinion of the Investigator.
- Has known active central nervous system (CNS) involvement.
- Continuance of toxicities due to prior radiotherapy or chemotherapy agents that do not recover to ≤ Grade 1 except alopecia or neuropathy.
- Failure to recover adequately, as judged by the investigator, from prior surgical procedures. Patients with active wound healing, patients who have had major surgery within 28 days from study entry, and patients who have had minor surgery within 14 days of study entry.
- Unstable angina, myocardial infarction, or a coronary revascularization procedure within 180 days of study entry.
- Active rheumatoid arthritis (RA), active inflammatory bowel disease, or any other disease or condition associated with chronic inflammation.
- Active infection requiring systemic antibiotic/ antifungal medication, known clinically active hepatitis B or C infection, or known HIV disease.
- Known or suspected Wilson's Disease, or other conditions that affect copper accumulation or regulation.
- Uncontrolled concurrent illness including, but not limited to: symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with the study requirements.
- The last treatment for the subject before signing the informed consent was bcl-2 targeted drug treatment (if the subject had received bcl-2 inhibitor treatment but did not develop drug resistance, it could be included in this study).
- History of secondary active malignancies within the past 2 years. However, adequately treated superficial skin cancer other than melanoma, in-situ cervix cancer more than 4 weeks, or prostate cancer not requiring any treatment and under surveillance prior to enrollment will not be considered exclusionary.
- Known to be allergic to study drug ingredients or their analogues.
- Pregnancy or lactation, or pregnancy is expected during the study period or within 3 months after the last administration of APG-2575.
- Any other condition or circumstance that would, in the opinion of the investigator, make the patient unsuitable for participation in the study.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: single-agent, open-label, Phase I study of APG-2575
The study consists of the dose escalation stage and the dose expansion stage
|
Multiple dose cohorts, PO, every day (QD) of a 28-day cycle
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Tolerated Dose (MTD)
Time Frame: 28 days
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Patients with APG-2575 treatment related adverse events (AE), serious adverse events (SAE) will be assessed according NCI CTCAE Version 5.0
|
28 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum plasma concentration (Cmax)
Time Frame: 28 days
|
Maximum plasma concentration (Cmax) will be assessed in the patients treated with APG-2575
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28 days
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Area under the plasma concentration versus time curve (AUC)
Time Frame: 28 days
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Area under the plasma concentration versus time curve (AUC) of APG-2575 will be assessed in the patients treated with APG-2575
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28 days
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Anti-tumor effects of APG-2575
Time Frame: up to 3 years
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Response will be evaluated every 2 cycles (8 weeks), by the investigator based on disease specific criteria.
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up to 3 years
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Jianxiang Wang, MD, Blood Diseases Hospital Chinese Academy of Medical Sciences
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 3, 2019
Primary Completion (Estimated)
December 31, 2024
Study Completion (Estimated)
December 31, 2025
Study Registration Dates
First Submitted
April 10, 2019
First Submitted That Met QC Criteria
April 11, 2019
First Posted (Actual)
April 12, 2019
Study Record Updates
Last Update Posted (Actual)
January 5, 2024
Last Update Submitted That Met QC Criteria
January 4, 2024
Last Verified
January 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Neoplasms by Site
- Disease Attributes
- Hematologic Diseases
- Leukemia
- Leukemia, B-Cell
- Chronic Disease
- Lymphoma
- Hematologic Neoplasms
- Lymphoma, Non-Hodgkin
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Lymphoid
Other Study ID Numbers
- APG-2575-CN-001
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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