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

NCT ID: NCT03537482

Last Updated: 2024-08-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-07
• Study Completion Date: 2025-02-15

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.

Detailed Description

APG-2575 will be administered orally, once daily for consecutive 4 weeks as one cycles. 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 DLT, two drug related Grade 2 toxicities or one drug related ≥ Grade 3 toxicity, or laboratory or clinical TLS, or suspected hypersensitivity reaction occur in Cycle 1, or dose level of 400 mg is reached, 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 is defined, a maximum of 20 patients will be treated at that dose level.

Conditions

Hematologic Malignancies

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

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

Group Type: EXPERIMENTAL

APG-2575

Intervention Type: DRUG

APG-2575 will be administered as an oral tablet

Interventions

APG-2575

APG-2575 will be administered as an oral tablet

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age ≥18 years old.

2. 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

3. 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.

4. Life expectancy ≥ 3 months.

5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): 0 -1 in dose escalation ; 0-2 in dose expansion.

6. QTc interval ≤450ms in males, and ≤470ms in females.

7. Adequate bone marrow function independent of growth factor:

8. Absolute neutrophil count (ANC) ≥1.0 X 109/L.

9. Hemoglobin ≥ 8.0 g/dL.

10. Platelets count ≥ 30 X 109/L (entry platelet count must be independent of transfusion within 7 days of first dose).

11. Adequate renal and liver function as indicated by:

Exclusion Criteria

1. Prior history of allogeneic cell transplant.

2. Subjects have been diagnosed with Burkitt's lymphoma, Burkitt-like lymphoma, or lymphoblastic lymphoma/leukemia.

3. Received chemotherapy within 14 days (42 days for nitrosoureas or mitomycin C) prior to entering the study.

4. Received biologic (< 28 days), small molecule targeted therapies (< 5 half-life) or other anti-cancer therapy within 21 days of study entry.

5. Radiation within 14 days of study entry, thoracic radiation within 28 days of study entry.

6. Has gastrointestinal conditions that could affect the absorption of APG-2575 in the opinion of the Investigator.

7. Has known active central nervous system (CNS) involvement.

8. Continuance of toxicities due to prior radiotherapy or chemotherapy agents that do not recover to ≤ Grade 1 except alopecia or neuropathy.

9. 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.

10. 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.

11. Unstable angina, myocardial infarction, or a coronary revascularization procedure within 180 days of study entry.

12. Active rheumatoid arthritis (RA), active inflammatory bowel disease, chronic infections, or any other disease or condition associated with chronic inflammation.

13. Active infection requiring systemic antibiotic/ antifungal medication, known clinically active hepatitis B or C infection, or on antiretroviral therapy for HIV disease.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ascentage Pharma Group Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yifan Zhai, MD, PhD

Role: STUDY_CHAIR

Ascentage Pharma Group Inc.

Locations

Mayo Clinic

Jacksonville, Florida, United States

Site Status: RECRUITING

Duke Unviersity

Durham, North Carolina, United States

Site Status: COMPLETED

MDACC

Houston, Texas, United States

Site Status: RECRUITING

St. Vincent Hospital

Fitzroy, Victoria, Australia

Site Status: RECRUITING

Epworth Healthcare

Richmond, Victoria, Australia

Site Status: RECRUITING

Countries

United States; Australia

Central Contacts

Laura Glass

Role: CONTACT

Laura.Glass@ascentage.com

301-520-5964

Facility Contacts

Sikander Ailawadhi, MD

Role: primary

s.ailawadhi@mayo.org

904-953-0853

Tapan Kadia, MD

Role: primary

tkadia@mdanderson.org

713-792-7734

lisa demosthenous

Role: primary

lisa.demosthenous@suha.org.au

61-3-9231-3630

andrew Karapetis, MD

Role: primary

a.karapetis@epworth.au.com

37-817-7762

Other Identifiers

APG2575-001

Identifier Type: -

Identifier Source: org_study_id