ICP-248 in Combination with Azacitidine in Treatment-Naïve Subjects with Acute Myelogenous Leukemia(AML) or Previously Treated Relapsed/Refractory Subjects with Acute Myelogenous Leukemia(R/R AML).

Recruitment & Eligibility

Status: NOT_YET_RECRUITING

Sex: All

Target Recruitment: 90

Inclusion Criteria

Eligible subjects must meet all of the following criteria:
1. Subject must have confirmation of diagnosis of AML, except for acute promyelocytic leukemia (APL) per 2016 World Health Organization (WHO) criteria.
2. Previously treated relapsed/refractory AML subjects per 2017 European Leukemia Net (ELN) criteria.
3. Treatment-naïve AML subjects should be:
  - ≥60 years of age;OR
  - <60 years will be eligible if the subject has at least one of the following co-morbidities, which make the subject unfit for intensive chemotherapy:
    1. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 2 - 3;
    2. History of congestive heart failure requiring treatment or Ejection Fraction (EF) ≤ 50% or chronic stable angina;
    3. Clinically significant respiratory failure or diffusing capacity for carbon monoxide (DLCO) ≤ 65% or forced expiratory volume in 1 second (FEV1)
      
      ≤ 65%;
    4. Creatinine clearance ≥ 30 mL/min to < 45 mL/min (calculated by Cockcroft Gault formula);
    5. Total bilirubin > 1.5 to ≤ 3.0 ×upper limit of normal (ULN);
    6. Any other comorbidity that the Investigator judges to be incompatible with intensive chemotherapy must be reviewed and approved by the Sponsor medical monitor before study enrollment.
4. Subject must have a projected life expectancy of at least 12 weeks.
5. Subject must have adequate renal function as demonstrated by a creatinine clearance≥ 30 mL/min; determined via urine collection for 24-hour creatinine clearance or by the Cockcroft-Gault formula.
6. Subject must have adequate liver function.

Exclusion Criteria

Previously treated subject, who are refractory to previous azacitidine-based therapy defined as failure to achieve CR/CRi/MLFS per 2017 ELN criteria or intolerable to previous azacitidine-based treatment defined as discontinuation from azacitidine-based therapy due to clearly documented toxicity.
Previously treated subject, who are refractory to previous BCL-2 inhibitor-based therapy defined as failure to achieve CR/CRi/MLFS per 2017 ELN criteria or intolerable to previous BCL-2 inhibitor-based treatment defined as discontinuation from BCL-2 inhibitor-based therapy due to clearly documented toxicity.
Subject has acute promyelocytic leukemia (French-American-British Class M3 AML) or AML with t(8;21)(q22;q22.1)/RUNX1::RUNX1T1.
Subject has known central nervous system (CNS) leukemia.
Subject has a history of myeloproliferative neoplasm (MPN) including polycythemia vera, myelofibrosis, essential thrombocythemia, or chronic myelogenous leukemia.
Subject has a white blood cell count > 25 × 109/L (Cytoreductive therapy for leucocytosis are permitted to meet this criterion).
The serologic status suggestive of active hepatitis B or C virus infection.
History of immunodeficiency, including a positive human immunodeficiency virus (HIV) antibody test.
Subjects have another active malignancy within the past 2 years before study entry, except for who have received curatively treated.
History of significant cardiovascular disease.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ICP-248 in combination with azacitidine	ICP-248	-
ICP-248 in combination with azacitidine	Azacitidine	-

Primary Outcome Measures

Name	Time	Method
Incidence, type, and severity of dose-limiting toxicity (DLT).	2.5 years
Recommended phase II dose (RP2D) and/or maximum tolerated dose (MTD).	2.5 years
The incidence, nature, and severity of adverse events (AEs) as assessed per National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE v5.0) criteria.	2.5 years
Composite complete remission rate by Investigator per ELN 2017 criteria.	2.5 years
Composite complete remission rate by completion of cycle 2 by Investigator per ELN 2017 criteria.	2.5 years

Secondary Outcome Measures

Name	Time	Method
Composite complete remission rate: The proportion of subjects with complete remission (CR) and CR with incomplete hematologic recovery (CRi) by Investigator per European Leukemia Net (ELN) 2017 criteria.	2.5 years
Composite complete remission rate by completion of cycle 2 by Investigator per ELN 2017 criteria.	2.5 years
The incidence, nature, and severity of adverse events (AEs) as assessed per NCI-CTCAE v5.0 criteria.	2.5 years
Maximum concentration (Cmax)of ICP-248.	2.5 years
Area under the curve (AUC) of ICP-248.	2.5 years
Time of maximum observed plasma(Tmax)of ICP-248.	2.5 years
Trough concentration(Ctrough) of ICP-248.	2.5 years
Apparent clearance (CL/F) of ICP-248.	2.5 years
Partial Response (PR) by investigator per ELN 2017 criteria.	2.5 years
Overall survival (OS) by investigator per ELN 2017 criteria.	2.5 years
Duration of Response (DOR) by investigator per ELN 2017 criteria.	2.5 years
Event-free Survival (EFS) by investigator per ELN 2017 criteria.	2.5 years
Relapse-free Survival (RFS) by investigator per ELN 2017 criteria.	2.5 years

ICP-248 in Combination with Azacitidine in Treatment-Naïve Subjects with Acute Myelogenous Leukemia(AML) or Previously Treated Relapsed/Refractory Subjects with Acute Myelogenous Leukemia(R/R AML).

Recruitment & Eligibility

Study & Design

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