A Study to Evaluate the Safety,PK and PD of APG-2575 in Patients With Hematologic Malignancies

NCT03913949 | Active Not Recruiting Phase 1

• 1 other identifier: APG-2575-CN-001
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Chronic Lymphocytic Leukemia; Non Hodgkin Lymphoma

Keywords

APG-2575; B-cell lymphoma 2 (BCL-2); Chronic lymphocytic leukemia; non-hodgkin's lymphoma

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  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 Outcomes (3)

• Maximum plasma concentration (Cmax)

  28 days

• Area under the plasma concentration versus time curve (AUC)

  28 days

• Anti-tumor effects of APG-2575

  up to 3 years

Study Arms (1)

single-agent, open-label, Phase I study of APG-2575

EXPERIMENTAL

The study consists of the dose escalation stage and the dose expansion stage

Drug: APG-2575

Interventions

APG-2575 DRUG

Multiple dose cohorts, PO, every day (QD) of a 28-day cycle

single-agent, open-label, Phase I study of APG-2575

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ascentage Pharma Group Inc.: lead
• Suzhou Yasheng Pharmaceutical Co., Ltd.: collaborator

Study Sites (5)

Anhui Procincial hospital

Hefei, Anhui, China

Location

Henan Provincial Oncology Hospital

Zhengzhou, Henan, China

Location

Zhongnan Hospital of Wuhan University

Wuhan, Hubei, China

Location

Blood Diseases Hospital Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, 300020, China

Location

The First Affiliated Hospital, Zhejiang University School of Medicin

Hangzhou, Zhejiang, China

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin

Interventions

Lisaftoclax

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; 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; Lymphoma

Study Officials

• Jianxiang Wang, MD

  Blood Diseases Hospital Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2019
• First Posted: April 12, 2019
• Study Start: June 3, 2019
• Primary Completion: October 20, 2024
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 1, 2026

Record last verified: 2026-04

Locations

CN (5)