Acute Myelogenous Leukemia, Myelodysplastic Syndromes (MDS)
Conditions
Brief summary
Evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ICP-248 in combination with azacitidine in patients with acute myelogenous leukemia and Myelodysplastic Syndromes.
Interventions
DRUGICP-248
Eligible patients will receive ICP-248 orally as per the protocol，once daily for every 28 days as one treatment cycle
DRUGAzacitidine
Eligible patients will receive azacitidine subcutaneously or intravenously as per the protocol，once daily on days 1-7 of each 28-day cycle.
Sponsors
Beijing InnoCare Pharma Tech Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 \[APL\]) or MDS per 2016 World Health Organization (WHO) criteria. 2. For AML (except for APL) cohort: 1. Previously treated relapsed/refractory AML subjects 2. 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 3. For MDS cohort: Adult TN MDS and R/R MDS: revised International Prognostic Scoring System (IPSS-R) score \> 3 and bone marrow blasts ≥ 5%. 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. R/R AML or R/R MDS with no response or intolerance to post azacitidine or BCL-2i. 2. Subject has acute promyelocytic leukemia (French-American-British Class M3 AML) . 3. Subject has known central nervous system (CNS) leukemia. 4. Suggest patients with active hepatitis B or C virus infection 5. History of immunodeficiency, including a positive human immunodeficiency virus (HIV) antibody test. 6. Subjects have another active malignancy within the past 2 years before study entry, except for curatively treated.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
| AML cohort:Composite complete remission rate by Investigator per ELN 2017 criteria. | 2.5 years |
| AML cohort：Composite complete remission rate by completion of cycle 2 by Investigator per ELN 2017 criteria. | 2.5 years |
| MDS cohort：mOR rate, including CR, mCR, and PR, assessed by Investigator at any time point during the study per revised IWG 2006 MDS Criteria. | 2.5 years |
Secondary
| Measure | Time frame |
|---|---|
| AML cohort：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 |
| AML cohort：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 |
| AML cohort：Partial Response (PR) by investigator per ELN 2017 criteria. | 2.5 years |
| AML cohort：Overall survival (OS) by investigator per ELN 2017 criteria. | 2.5 years |
| AML cohort：Duration of Response (DOR) by investigator per ELN 2017 criteria. | 2.5 years |
| AML cohort：Event-free Survival (EFS) by investigator per ELN 2017 criteria. | 2.5 years |
| AML cohort：Relapse-free Survival (RFS) by investigator per ELN 2017 criteria. | 2.5 years |
| AML cohort：Morphologic leukemia-free state (MLFS) by investigator per ELN 2017 criteria. | 2.5 years |
| MDS cohort：Modified overall response (mOR) rate, including CR, marrow complete response (mCR), and PR, assessed by Investigator at any time point during the study per revised International Working Group (IWG) 2006 MDS Criteria | 2.5 years |
| MDS cohort：Complete remission(CR) rate by Investigator per revised IWG 2006 MDS Criteria | 2.5 years |
| MDS cohort：Event-free survival (EFS) by Investigator per revised IWG 2006 MDS Criteria | 2.5 years |
| MDS cohort：Duration of modified overall response (DmOR) by Investigator per revised IWG 2006 MDS Criteria | 2.5 years |
| MDS cohort：Overall survival(OS) by Investigator per revised IWG 2006 MDS Criteria | 2.5 years |
| MDS cohort：Marrow complete response (mCR) rate by Investigator per revised IWG 2006 MDS Criteria | 2.5 years |
Countries
China, United States
Contacts
CONTACTAlexia Lu
Outcome results
None listed