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).

InnoCare Pharma

Status and phase

Enrolling

Phase 1

Conditions

Acute Myelogenous Leukemia

Treatments

Drug: Azacitidine

Drug: ICP-248

Study type

Interventional

Funder types

Industry

Identifiers

NCT06656494

ICP-CL-01205

Details and patient eligibility

About

Evaluate the safety, tolerability , pharmacokinetics , and preliminary efficacy of ICP-248 in Combination with azacitidine in Patients with Acute Myelogenous Leukemia . This study consists of two parts: Part 1 dose escalation period and Part 2 dose expansion period.

Enrollment

102 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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
  - ≥18 years and <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.