APG-2575 Study of Safety, Tolerability ,PK/PD in Patients With Hematologic Malignancies

NCT03537482 | Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: APG2575-001
• Study Type: interventional
• Target: 90
• Locations: 2 countries
• Sites: 5

Brief Summary

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.

Conditions

Hematologic Malignancies

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 4.0

  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 2 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

APG-2575 will be administered as an oral tablet

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 either one of the B-cell hematologic malignancies including multiple myeloma, chronic lymphocytic leukemia, lymphoplasmacytic lymphoma, and non-Hodgkin's lymphoma such as mantle cell lymphoma, diffuse large B cell lymphoma, Waldenstrom macroglobulinemia (WM) and acute myeloid leukemia
• Patient must have relapsed or refractory to, intolerant to, or are considered ineligible for therapies known to provide clinical benefit. In addition,
• a. AML Patients will be eligible if they have failed standard induction regimen, are not considered candidate for further chemotherapy or stem cell transplantation or have primary refractory AML.
• Life expectancy ≥ 3 months.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): 0 -1 in dose escalation ; 0-2 in dose expansion.
• QTc interval ≤450ms in males, and ≤470ms in females.
• Adequate bone marrow function independent of growth factor:
• Absolute neutrophil count (ANC) ≥1.0 X 109/L.
• Hemoglobin ≥ 8.0 g/dL.
• Platelets count ≥ 30 X 109/L (entry platelet count must be independent of transfusion within 7 days of first dose).
• Adequate renal and liver function as indicated by:

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 (42 days for nitrosoureas or mitomycin C) 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.
• 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.
• 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.
• 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, chronic infections, 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 on antiretroviral therapy for HIV disease.

Sponsors & Collaborators

• Ascentage Pharma Group Inc.: lead

Study Sites (5)

Mayo Clinic

Jacksonville, Florida, 32224, United States

RECRUITING

Duke Unviersity

Durham, North Carolina, 27701, United States

COMPLETED

MDACC

Houston, Texas, 77030, United States

RECRUITING

St. Vincent Hospital

Fitzroy, Victoria, 3065, Australia

RECRUITING

Epworth Healthcare

Richmond, Victoria, 3121, Australia

RECRUITING

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

Lisaftoclax

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Yifan Zhai, MD, PhD

  Ascentage Pharma Group Inc.

  STUDY CHAIR

Central Study Contacts

Laura Glass

CONTACT

301-520-5964; Laura.Glass@ascentage.com

Study Design

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

Model Details: dose escalation and dose expansion after MTD

Study Record Dates

• First Submitted: March 27, 2018
• First Posted: May 25, 2018
• Study Start: August 7, 2018
• Primary Completion: September 15, 2024
• Study Completion: February 15, 2025
• Last Updated: August 19, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (3); AU (2)