RECRUITING

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

Conditions

AML Acute Myeloid Leukemia Chronic Myelomonocytic Leukemia CMML Myelodysplastic Syndromes High-risk Myelodysplastic Syndrome MDS TP53

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2020-12-04

Study Completion:2025-12-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04358393

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.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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. 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	Pregnancy or breastfeeding Severe psychiatric disorders Active substance abuse Unstable medical conditions Inability to comply with study requirements

Inclusion Criteria

Exclusion 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.
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

Pregnancy or breastfeeding
Severe psychiatric disorders
Active substance abuse
Unstable medical conditions
Inability to comply with study requirements

Contacts and Locations

Study Contact

Angela Kaiser

CONTACT

301-509-0357

Angela.Kaiser@ascentage.com

Principal Investigator

Yifan Zhai, MD, PhD

STUDY_CHAIR

Ascentage Pharma Group Inc.

Study Locations (Sites)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234

United States

Rocky Mountain Cancer Centers

Denver, Colorado, 80218

United States

Duke University

Durham, North Carolina, 27710

United States

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246

United States

MD Anderson

Houston, Texas, 77030

United States

Texas Oncology - Tyler

Tyler, Texas, 75702

United States

Virginia Cancer Specialists

Fairfax, Virginia, 22031

United States

Seattle Cancer Care Alliance

Seattle, Washington, 98109

United States

Collaborators and Investigators

Sponsor: Ascentage Pharma Group Inc.

Yifan Zhai, MD, PhD, STUDY_CHAIR, 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 Registration Dates

Study Start Date2020-12-04

Study Completion Date2025-12-30

Study Record Updates

Study Start Date2020-12-04

Study Completion Date2025-12-30

Terms related to this study

Keywords Provided by Researchers

TP53

Additional Relevant MeSH Terms

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