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

January 30, 2024 updated by: Ascentage Pharma Group Inc.

A Phase Ib/II Study of APG-115 Alone or in Combination With Azacitidine in Patients With Relapse/Refractory AML, CMML or MDS

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Part 1: Dose escalation of APG-115 will use standard 3+3 design. APG-115 is administered orally once daily (QD) on Day 1-5 every 28-day cycle. The starting target dose is 100 mg (dose level; DL1) and will be increased in subsequent cohorts to 150 mg (DL2), 200 mg (DL3), and 250 mg (DL4), accordingly.

Part 2: Dose escalation of APG-115 in combination with 5-AZA will use standard 3+3 design. 5-AZA is administered at 75 mg/m˄2/d subcutaneously daily on Day 1-7 every 28 days.

Study Type

Interventional

Enrollment (Estimated)

69

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Arizona
      • Gilbert, Arizona, United States, 85234
        • Recruiting
        • Banner MD Anderson Cancer Center
        • Principal Investigator:
          • Matthew Ulrickson, MD
        • Contact:
    • Colorado
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Recruiting
        • Duke University
        • Contact:
        • Principal Investigator:
          • Harry Erba, MD, PhD
    • Texas
      • Dallas, Texas, United States, 75246
      • Houston, Texas, United States, 77030
        • Recruiting
        • MD Anderson
        • Contact:
        • Principal Investigator:
          • Tapan Kadia, MD
      • Tyler, Texas, United States, 75702
    • Virginia
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • Seattle Cancer Care Alliance
        • Principal Investigator:
          • Mary-Elizabeth Percival, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. 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.

  2. Adequate organ function as defined below:

    1. Liver function (total bilirubin < or = 1.5 x upper limit of normal (ULN), aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) <3 x ULN
    2. 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)
    3. Known cardiac ejection fraction of > or = 45% within the past 3 months
  3. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
  4. A negative serum pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.
  5. 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.
  6. Subject must have a projected life expectancy of at least 12 weeks.
  7. Subject has a white blood cell count < 25 × 10˄9/L. Note: Hydroxyurea is permitted to meet this criteria.

Exclusion:

  1. Pregnant women are excluded.
  2. 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.
  3. 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.
  4. Have acute promyelocytic leukemia.
  5. Active infection requiring systemic antibiotic/antifungal medication, known clinically active hepatitis B or C, or HIV infection.
  6. 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.
  7. Documented hypersensitivity to any of the components of the therapy program
  8. Active, uncontrolled central nervous system (CNS) leukemia will not be eligible.
  9. 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.
  10. Any prior systemic MDM2-p53 inhibitor treatment
  11. Any other condition or circumstance that would, in the opinion of the investigator, make the patient unsuitable for participation in the study.

  12. History of other malignancies within 2 years prior to study entry, with the exception of:

    1. Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast
    2. Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin
    3. Previous malignancy confined and surgically resected (or treated with other modalities) with curative intention: requires discussion with sponsor
  13. Failure to have recovered (Grade > 1) from prior treatment (including chemotherapy, targeted therapy, immunotherapy, experimental agents, radiation, or surgery)
  14. Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree atrioventricular (AV) block type II, 3rd degree block, or corrected QT interval (QTc) ≥470 msec

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: APG-115 monotherapy
Monotherapy given in part 1
Drug: APG-115
APG-115 given once daily on day 1-5 of every 28 day cycle
Experimental: APG-115 + 5-azacitidine combination
Combination therapy given in part 2
Drug: APG-115
APG-115 given once daily on day 1-5 of every 28 day cycle
Drug: 5-azacitidine
5-AZA is given at 75 mg/m˄2/d subcutaneously daily on Day 1-7 every 28 days
Other Names:
  • Vidaza
  • Azadine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose
Time Frame: 28 days
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ascentage Pharma Group Inc.

Investigators

  • Study Chair: Yifan Zhai, MD, PhD, Ascentage Pharma Group Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 4, 2020

Primary Completion (Estimated)

December 30, 2024

Study Completion (Estimated)

December 30, 2025

Study Registration Dates

First Submitted

April 21, 2020

First Submitted That Met QC Criteria

April 21, 2020

First Posted (Actual)

April 24, 2020

Study Record Updates

Last Update Posted (Estimated)

February 1, 2024

Last Update Submitted That Met QC Criteria

January 30, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • APG115AU101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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