This study is a clinical trial to evaluate the tolerability and pharmacokinetics of TQB3455 tablets in patients with hematological malignancies. TQB3455 is an isocitrate dehydrogenase 2(IDH2) inhibitor . This project is divided into two stages. The first stage aims to evaluate the safety and tolerability of single or multiple oral administration of TQB3455 tablets in subjects with malignant hematological tumors. The second phase aims to evaluate the efficacy and safety of TQB3455 tablets alone or in combination with azacitidine in subjects with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
100
TQB3455 is a selective IDH2 mutant enzyme inhibitor. Azacitidine for injection is a cytosine nucleoside drug that is used for demethylation therapy.
Peking University People's Hospital
Beijing, Beijing Municipality, China
RECRUITINGPeking University international Hospital
Beijing, Beijing Municipality, China
NOT_YET_RECRUITINGThe Second Hospital of Hebei Medical University
Shijiazhuang, Hebei, China
NOT_YET_RECRUITINGHarbin The First Hospital
Harbin, Heilongjiang, China
NOT_YET_RECRUITINGShanghai Sixth People's Hospital
Shanghai, Shanghai Municipality, China
NOT_YET_RECRUITINGWest China Hospital of Sichuan University
Chengdu, Sichuan, China
NOT_YET_RECRUITINGPeople's Hospital of Tianjin
Tianjin, Tianjin Municipality, China
NOT_YET_RECRUITINGDose-limiting toxicity (DLT)
Subjects appear the toxic reaction relate to the drug after treatment within 28 days.
Time frame: Baseline up to 28 days
The maximum tolerated dose (MTD)
The highest dose at which no more than 33% of the subjects experience a dose-limiting toxicity (DLT) during treatment.
Time frame: Up to 48 weeks
Overall Remission Rate
The number of participants with CR + incomplete recovery (CRi) + incomplete platelet recovery (CRp) according to modified International Working Group Acute Myeloid Leukemia (IWG AML) response criteria.
Time frame: Up to 48 weeks
Overall survival (OS)
Overall survival defined as the time from enrollment to death from any cause.
Time frame: U to 96 weeks
Duration of Response (DOR)
DOR will be defined as median number of months from date of first documented objective response until first documented sign of disease progression or death due to any causes.
Time frame: Up to 48 weeks
Complete Remission Rate
The number of participants with morphologic complete remission (CR) according to modified International Working Group Acute Myeloid Leukemia Response Criteria (IWG AML).
Time frame: Up to 48 weeks
Cmax
Cmax is the maximum plasma concentration of TQB3455 or metabolite(s).
Time frame: Hour 0, 0.25, 0.5, 1, 2, 3, 5, 8, 10, 12, 24, 48, 96, 144 hours post-dose on single dose; Hour 0 of day 8, day 15, day 22 on multiple dose and hour 0, 0.25, 0.5, 1, 2, 3, 5, 8, 12, 24 hours post-dose on multiple dose of day 28
Tmax
To characterize the pharmacokinetics of TQB3455 by assessment of time to reach maximum plasma concentration.
Time frame: Hour 0, 0.25, 0.5, 1, 2, 3, 5, 8, 10, 12, 24, 48, 96, 144 hours post-dose on single dose; Hour 0 of day 8, day 15, day 22 on multiple dose and hour 0, 0.25, 0.5, 1, 2, 3, 5, 8, 12, 24 hours post-dose on multiple dose of day 28
Area Under the Curve (AUC) 0-t
To characterize the pharmacokinetics of TQB3455 by assessment of area under the plasma concentration time curve from zero to infinity.
Time frame: Hour 0, 0.25, 0.5, 1, 2, 3, 5, 8, 10, 12, 24, 48, 96, 144 hours post-dose on single dose; Hour 0 of day 8, day 15, day 22 on multiple dose and hour 0,0.25, 0.5, 1, 2, 3, 5, 8, 12, 24 hours post-dose on multiple dose of day 28
α-Hydroxyglutaric acid (2-HG)
The concentration of 2-HG.
Time frame: Day 1, Day 8 and Day 15 pre-dose on cycle 1; Day1, Day15 pre-dose on cycle 2 ; Day 1 pre-dose on multiple dose from cycle 3 to cycle 8. Each cycle is 28 days.
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