- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04358393
A Study of APG-115 Alone or Combined With Azacitidine in Patients With AML, CMML, or MDS
A Phase Ib/II Study of APG-115 Alone or in Combination With Azacitidine in Patients With Relapse/Refractory AML, CMML or MDS
Study Overview
Status
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
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Angela Kaiser
- Phone Number: 301-509-0357
- Email: Angela.Kaiser@ascentage.com
Study Locations
-
-
Arizona
-
Gilbert, Arizona, United States, 85234
- Recruiting
- Banner MD Anderson Cancer Center
-
Principal Investigator:
- Matthew Ulrickson, MD
-
Contact:
- Kevin Minahan
- Phone Number: 480-256-5463
- Email: Kevin.Minahan@bannerhealth.com
-
-
Colorado
-
Denver, Colorado, United States, 80218
- Recruiting
- Rocky Mountain Cancer Centers
-
Contact:
- Patricia Gibson
- Email: Patricia.Gibson@usoncology.com
-
Contact:
- Kathryn Wilson
- Email: Kathryn.Wilson@usoncology.com
-
Principal Investigator:
- Christopher Benton, MD
-
-
North Carolina
-
Durham, North Carolina, United States, 27710
- Recruiting
- Duke University
-
Contact:
- Christine Daly
- Phone Number: 919-660-2077
- Email: christine.daly@duke.edu
-
Principal Investigator:
- Harry Erba, MD, PhD
-
-
Texas
-
Dallas, Texas, United States, 75246
- Recruiting
- Texas Oncology - Baylor Charles A. Sammons Cancer Center
-
Contact:
- Catinna Mallett
- Email: catinna.mallett@usoncology.com
-
Contact:
- Jonathan Huntzinger
- Email: Jonathan.huntzinger@usoncology.com
-
Principal Investigator:
- Moshe Levy, MD
-
Houston, Texas, United States, 77030
- Recruiting
- MD Anderson
-
Contact:
- Tapan Kadia, MD
- Phone Number: 713-563-3534
- Email: tkadia@mdanderson.org
-
Principal Investigator:
- Tapan Kadia, MD
-
Tyler, Texas, United States, 75702
- Recruiting
- Texas Oncology - Tyler
-
Contact:
- Penny Watkins
- Email: Penny.Watkins@usoncology.com
-
Principal Investigator:
- Habte Yimer, MD
-
-
Virginia
-
Fairfax, Virginia, United States, 22031
- Recruiting
- Virginia Cancer Specialists
-
Contact:
- Lilliana Payne
- Email: lilliana.payne@usoncology.com
-
Contact:
- Hunfa Asghar
- Email: Hunfa.Asghar@usoncology.com
-
Principal Investigator:
- Mitul Gandhi, MD
-
-
Washington
-
Seattle, Washington, United States, 98109
- Recruiting
- Seattle Cancer Care Alliance
-
Principal Investigator:
- Mary-Elizabeth Percival, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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.
Exclusion:
- 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
- Failure to have recovered (Grade > 1) from prior treatment (including chemotherapy, targeted therapy, immunotherapy, experimental agents, radiation, or surgery)
- 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
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
|
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
|
APG-115 given once daily on day 1-5 of every 28 day cycle
5-AZA is given at 75 mg/m˄2/d subcutaneously daily on Day 1-7 every 28 days
Other Names:
|
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
Sponsor
Investigators
- Study Chair: Yifan Zhai, MD, PhD, Ascentage Pharma Group Inc.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Disease Attributes
- Disease
- Bone Marrow Diseases
- Hematologic Diseases
- Precancerous Conditions
- Myelodysplastic-Myeloproliferative Diseases
- Leukemia, Myeloid
- Chronic Disease
- Syndrome
- Myelodysplastic Syndromes
- Leukemia
- Preleukemia
- Leukemia, Myelomonocytic, Chronic
- Leukemia, Myelomonocytic, Juvenile
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Azacitidine
Other Study ID Numbers
- APG115AU101
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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.
Clinical Trials on Acute Myeloid Leukemia
-
University of PennsylvaniaActive, not recruitingAcute Myeloid Leukemia, in Relapse | Acute Myeloid Leukemia, Refractory | Acute Myeloid Leukemia, PediatricUnited States
-
Terrence J Bradley, MDImago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New...RecruitingAcute Myeloid Leukemia | Refractory Acute Myeloid Leukemia | Acute Myeloid Leukemia, in RelapseUnited States
-
National Cancer Institute (NCI)RecruitingAcute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Recurrent Acute Myeloid Leukemia | Refractory Acute Myeloid LeukemiaUnited States
-
Bhavana BhatnagarCTI BioPharmaCompletedRecurrent Adult Acute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Untreated Adult Acute Myeloid Leukemia | Therapy-Related Acute Myeloid LeukemiaUnited States
-
Washington University School of MedicineWithdrawnRefractory Acute Myeloid Leukemia | Relapsed Acute Myeloid LeukemiaUnited States
-
C. Babis AndreadisGateway for Cancer Research; AVEO Pharmaceuticals, Inc.TerminatedAcute Myeloid Leukemia | Refractory Acute Myeloid Leukemia | Relapsed Acute Myeloid LeukemiaUnited States
-
Jacqueline Garcia, MDEli Lilly and CompanyCompletedCombination Merestinib and LY2874455 for Patients With Relapsed or Refractory Acute Myeloid LeukemiaRelapsed Adult Acute Myeloid Leukemia | Refractory Adult Acute Myeloid LeukemiaUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)RecruitingAcute Myeloid Leukemia | Recurrent Adult Acute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Refractory Acute Myeloid LeukemiaUnited States
-
University of NebraskaNational Cancer Institute (NCI)Active, not recruitingSecondary Acute Myeloid Leukemia | Therapy-Related Acute Myeloid Leukemia | Adult Acute Myeloid LeukemiaUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)Active, not recruitingAcute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Untreated Adult Acute Myeloid Leukemia | Recurrent Acute Myeloid Leukemia | Refractory Acute Myeloid Leukemia | Therapy-Related Acute Myeloid LeukemiaUnited States
Clinical Trials on APG-115
-
Ascentage Pharma Group Inc.RecruitingT-Prolymphocytic LeukemiaUnited States
-
Ascentage Pharma Group Inc.Suzhou Yasheng Pharmaceutical Co., Ltd.RecruitingSolid Tumor | NeuroblastomaChina
-
Ascentage Pharma Group Inc.CompletedPatients With Advanced Solid Tumor or LymphomaUnited States
-
Ascentage Pharma Group Inc.Suzhou Yasheng Pharmaceutical Co., Ltd.RecruitingAdvanced Solid Tumor | LiposarcomaChina
-
University of Michigan Rogel Cancer CenterAscentage Pharma Group Inc.SuspendedSalivary Gland Cancer | Malignant Salivary Gland CancerUnited States
-
Ascentage Pharma Group Inc.Merck Sharp & Dohme LLCRecruitingMelanoma | P53 Mutation | Uveal Melanoma | Cutaneous Melanoma | Mucosal Melanoma | Malignant Peripheral Nerve Sheath Tumors | MPNST | Unresectable or Metastatic Melanoma or Advanced Solid Tumors | MDM2 Gene MutationUnited States, Australia
-
Ascentage Pharma Group Inc.CompletedSmall Cell Lung Cancer | Solid TumorUnited States
-
Ascentage Pharma Group Inc.Suzhou Yasheng Pharmaceutical Co., Ltd.RecruitingEsophageal Cancer | Ovarian Cancer | Non Small Cell Lung Cancer | Malignant Pleural Mesothelioma | Advanced Solid CancerChina
-
Gilead SciencesTerminatedNon-Hodgkin's Lymphoma | Chronic Lymphocytic LeukemiaUnited States
-
Ascentage Pharma Group Inc.Suzhou Yasheng Pharmaceutical Co., Ltd.TerminatedSmall Cell Lung Cancer and Other Solid TumorsChina