A Study of APG-2575 in Combination With Azacitidine in Patients With Acute Myeloid Leukemia (AML)

NCT04964518 | Unknown Phase 1 FDA Drug

• 1 other identifier: APG2575AU101
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 9

Brief Summary

This is a Phase Ib/II, open-label, multi-center study evaluating the safety, tolerability, efficacy and PK of APG-2575 in combination with Azacitidine in the patients with AML/MPAL or MDS/CMML. The study consists of dose escalation (Part I) and dose expansion phase (Part II)

Conditions

AML, Adult

Outcome Measures

Primary Outcomes (1)

• DLT

  Dose-limiting toxicity (DLT) rate at each dose level DLT will be assessed within the first 28-day cycle of study treatment via CTCAE version 5.0

  28 days

Study Arms (1)

APG2575 + Azacitidine

EXPERIMENTAL

200 mg APG2575 dose ramp up +AZA

Drug: APG 2575 ramp up arm

Interventions

APG 2575 ramp up arm DRUG

APG2575 ramp up + Azacitidine

Also known as: APG2575

APG2575 + Azacitidine

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with a diagnosis of histologically confirmed relapsed or refractory (R/R) acute myeloid leukemia (AML) or mixed phenotype acute leukemia (MPAL) or Chronic Myelomonocytic Leukemia (CMML) or relapsed/refractory Higher-Risk MDS by 2016 WHO classification for which no available standard therapies are indicated or anticipated to result in a durable response.
• MPAL will include biphenotypic leukemia, bilineal leukemia, undifferentiated leukemia, mixed lineage leukemia, leukemia of ambiguous lineage, T/myeloid leukemia, B/myeloid leukemia, or other diagnosis indicating the presence of multiple lineages within the cell population.
• Relapsed/refractory MDS will be defined as prior receipt of 4 cycles of HMA therapy with failure to attain a response, or progression of disease or relapse at any time after prior response to HMA therapy with Overall Revised International Prognostic Scoring System (IPSS-R) score \> 3 (intermediate, high or very high).

You may not qualify if:

• Pregnant women.
• Uncontrolled intercurrent illness including, but not limited to active uncontrolled infection, symptomatic congestive heart failure (NYHA Class III or IV), unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Have had leukemia therapy within 14 days prior to starting investigational drug.
• However, patients with rapidly proliferative disease may receive hydroxyurea as needed until 24 hours prior to starting therapy on this protocol and during the first cycle of study.
• Have taken strong inhibitors or inducers of CYP3A4 within 7 days prior to the first dose of APG-2575.
• Have acute promyelocytic leukemia (French-American-British Class M3 AML or WHO classification APL with PML-RARA) or AML/MPAL with BCR-ABL1 positive.
• Active infection requiring systemic antibiotic/antifungal medication, known clinically active hepatitis B or C, or HIV infection or active COVID-19. (Patients who have received COVID-19 vaccination will be considered as eligible for the study.)
• Have active/ongoing graft-versus host disease (GVHD) or require continued treatment with systemic immunosuppressive agents (calcineurin inhibitors within 4 weeks prior to the first dose).
• Myeloablative therapy with autologous or allogeneic hematopoietic stem cell rescue within 6 months of study treatment initiation.
• Documented hypersensitivity to any of the components of the therapy program.
• Active, uncontrolled CNS leukemia.
• Men and women of childbearing potential who do not practice contraception. Women of childbearing potential and men must agree to use at least 1 form of barrier birth control (such as condom) prior to study entry and for the duration of study participation.
• History of other malignancies within 2 years prior to study entry, with the exception of:
• Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast.
• Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin.

Sponsors & Collaborators

• Ascentage Pharma Group Inc.: lead

Study Sites (9)

UCLA Medical cetner Division of Hematology

Los Angeles, California, 94101, United States

RECRUITING

Novant Health

Charlotte, North Carolina, 28413, United States

RECRUITING

Novant Health

Winston-Salem, North Carolina, 27103, United States

RECRUITING

MDACC

Houston, Texas, 77030, United States

RECRUITING

Swedish Medical Center

Seattle, Washington, 98104, United States

RECRUITING

Pindara Private Hospital

Benowa, Queensland, 4217, Australia

RECRUITING

Sunshine Coast University Hospital

Birtinya, Queensland, 4575, Australia

RECRUITING

The Northern Hospital

Epping, Victoria, 3076, Australia

RECRUITING

Royal Perth Hospital

Perth, Western Aus, 6000, Australia

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Lisaftoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Qian Niu, MD

  Ascentage Pharma

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Angela Kaiser

CONTACT

301-509-0357; angela.kaiser@ascentage.com

Study Design

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

Model Details: 3+3 dose escalation

Study Record Dates

• First Submitted: June 23, 2021
• First Posted: July 16, 2021
• Study Start: July 30, 2021
• Primary Completion: July 30, 2024
• Study Completion: October 30, 2024
• Last Updated: October 25, 2023

Record last verified: 2023-10

Locations

US (5); AU (4)