A Study of APG-115 Alone or Combined With Azacitidine in Patients With AML, CMML, or MDS

NCT04358393 | Unknown Phase 1 FDA Drug

• 1 other identifier: APG115AU101
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 8

Brief Summary

This is a two Part study in patients with relapsed/refractory acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), or high risk myelodysplastic syndrome (MDS) that will initially evaluate the safety and tolerability of APG-115 as a single agent in Part 1, followed by a combination of APG-115 + 5-azacitidine (5-AZA) in Part 2.

Conditions

AML; Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia; CMML; Myelodysplastic Syndromes; High-risk Myelodysplastic Syndrome; MDS

Keywords

TP53

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose

  Part I is to assess the safety and tolerability of APG-115 by assessing the dose-limiting toxicity (DLT) of APG-115. End points include: Incidence of DLTs during the first 3 weeks of treatment of each dose cohort; Severity and frequency of any adverse event(s) (AE) and serious adverse event(s) (SAE) based on NCI CTCAE 5.0

  28 days

Study Arms (2)

APG-115 monotherapy

EXPERIMENTAL

Monotherapy given in part 1

Drug: APG-115

APG-115 + 5-azacitidine combination

EXPERIMENTAL

Combination therapy given in part 2

Drug: APG-115; Drug: 5-azacitidine

Interventions

APG-115 DRUG

APG-115 given once daily on day 1-5 of every 28 day cycle

APG-115 + 5-azacitidine combination; APG-115 monotherapy

5-azacitidine DRUG

5-AZA is given at 75 mg/m˄2/d subcutaneously daily on Day 1-7 every 28 days

Also known as: Vidaza, Azadine

APG-115 + 5-azacitidine combination

Eligibility Criteria

• Age: 18 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 AML, CMML, or high-risk MDS (overall revised international prognostic scoring system (IPSS-R) score \> 3, including intermediate, high, or very high risk) by World Health Organization (WHO) classification for which no available standard therapies are indicated or anticipated to result in a durable response.
• Adequate organ function as defined below:
• Liver function (total bilirubin \< or = 1.5 x upper limit of normal (ULN), aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \<3 x ULN
• Kidney function (defined as a calculated creatinine clearance ≥ 60 mL/min; determined via urine collection for 24-hour creatinine clearance or by the Cockcroft Gault formula)
• Known cardiac ejection fraction of \> or = 45% within the past 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• A negative serum pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.
• Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient or legally authorized representative is required prior to their enrollment on the protocol.
• Subject must have a projected life expectancy of at least 12 weeks.
• Subject has a white blood cell count \< 25 × 10˄9/L. Note: Hydroxyurea is permitted to meet this criteria.

You may not qualify if:

• Pregnant women are excluded.
• 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 for 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 acute promyelocytic leukemia.
• Active infection requiring systemic antibiotic/antifungal medication, known clinically active hepatitis B or C, or HIV infection.
• Have received allogeneic hematopoietic stem cell transplant (HSCT) within 12 months prior to the first dose, or who 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), or received autologous hematopoietic stem cell transplantation within 6 months prior to the first dose.
• Documented hypersensitivity to any of the components of the therapy program
• Active, uncontrolled central nervous system (CNS) leukemia will not be eligible.
• 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.
• Any prior systemic MDM2-p53 inhibitor treatment
• Any other condition or circumstance that would, in the opinion of the investigator, make the patient unsuitable for participation in the study.
• 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
• Previous malignancy confined and surgically resected (or treated with other modalities) with curative intention: requires discussion with sponsor

Sponsors & Collaborators

• Ascentage Pharma Group Inc.: lead

Study Sites (8)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

RECRUITING

Rocky Mountain Cancer Centers

Denver, Colorado, 80218, United States

RECRUITING

Duke University

Durham, North Carolina, 27710, United States

RECRUITING

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

RECRUITING

MD Anderson

Houston, Texas, 77030, United States

RECRUITING

Texas Oncology - Tyler

Tyler, Texas, 75702, United States

RECRUITING

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

RECRUITING

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes

Interventions

Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Yifan Zhai, MD, PhD

  Ascentage Pharma Group Inc.

  STUDY CHAIR

Central Study Contacts

Angela Kaiser

CONTACT

301-509-0357; Angela.Kaiser@ascentage.com

Study Design

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

Study Record Dates

• First Submitted: April 21, 2020
• First Posted: April 24, 2020
• Study Start: December 4, 2020
• Primary Completion: December 30, 2024
• Study Completion: December 30, 2025
• Last Updated: February 1, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)