Clinical Trials /

A Study of APG-115 Alone or in Combination With Azacitidine in Patients With Acute Myeloid Leukemia (AML)

NCT04358393

Description:

To determine the safety and tolerability of APG-115 combined with 5-azacytidine (5-AZA) in patients with R/R AML

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of APG-115 Alone or in Combination With Azacitidine in Patients With Acute Myeloid Leukemia (AML)
  • Official Title: A Phase Ib/II Study of APG-115 Alone or in Combination With Azacitidine in Patients With Relapse/Refractory AML

Clinical Trial IDs

  • ORG STUDY ID: APG115AU101
  • NCT ID: NCT04358393

Conditions

  • AML
  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
APG-115APG-115 + 5-azacytidine combination
5-azacytidineAPG-115 + 5-azacytidine combination

Purpose

To determine the safety and tolerability of APG-115 combined with 5-azacytidine (5-AZA) in patients with R/R AML

Detailed Description

      This is a two-part study that will initially evaluate the safety and tolerability of APG-115
      as a single age in Part 1, followed by a combination of APG-115 plus 5-AZA in part 2.

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

Trial Arms

NameTypeDescriptionInterventions
APG-115 monotherapyExperimentalMonotherapy given in part 1
  • APG-115
APG-115 + 5-azacytidine combinationExperimentalCombination therapy given in part 2
  • APG-115
  • 5-azacytidine

Eligibility Criteria

        Inclusion Criteria:

          1. Patients with a diagnosis of histologically confirmed relapsed or refractory (R/R)
             acute myeloid leukemia 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 <= 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose
Time Frame:28 days
Safety Issue:
Description: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

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Ascentage Pharma Group Inc.

Last Updated

January 28, 2021