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).

Conditions: Acute Myelogenous Leukemia

Summary: 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.


Eligibility criteria:
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: 1. 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. 2. 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. 3. subject has acute promyelocytic leukemia (french-american-british class m3 aml) or aml with t(8;21)(q22;q22.1)/runx1::runx1t1. 4. subject has known central nervous system (cns) leukemia. 5. subject has a history of myeloproliferative neoplasm (mpn) including polycythemia vera, myelofibrosis, essential thrombocythemia, or chronic myelogenous leukemia. 6. subject has a white blood cell count \> 25 × 109/l (cytoreductive therapy for leucocytosis are permitted to meet this criterion). 7. the serologic status suggestive of active hepatitis b or c virus infection. 8. history of immunodeficiency, including a positive human immunodeficiency virus (hiv) antibody test. 9. subjects have another active malignancy within the past 2 years before study entry, except for who have received curatively treated. 10. history of significant cardiovascular disease.