It's a double-blind , randomized ,multi-center study. The purpose of this study is to explore the efficacy and safety of flumatinib 400mg once daily (QD) versus 600mg QD as the first line therapy in patients with chronic myleiod leukemia(CML) in chronic phase(CP).
This is a dose-optimization study of flumatinib in adult patient with newly diagnosed CML-CP. The objective of this study is to compare the efficacy and safety of flumatinib 400mg QD with that of 600mg QD. Eligible patients are randomized in a 1:1 ratio to receive either fluamtinib 400mg QD or flumatinib 600mg QD. Randomization is stratified based on Sokal risk score (\<0.8,0.8\~1.2,\>1.2). Patients will discontinue study therapy due to treatment failure, disease progression or intolerance to study medication or due to investigator's or participant's decision. The primary efficacy endpoint is the rate of early molecular response , as measured by RQ-PCR at 3 months. Hematologic response, molecular response and cytogenetic response will be assessed at baseline and a certain frequency after treatment, until study completion.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
200
Flumatinib 400mg +Placebo for flumatinib are administered orally daily. Patients are randomized to flumatinib 400mg QD.
Flumatinib 600mg is administered orally daily. Patients are randomized to flumatinib 600mg QD.
Institute of Hematology and Oncology, Harbin The First Hospital
Harbin, Hei Longjiang, China
RECRUITINGEarly molecular response(EMR) rate at 3 months
Molecular response is assessed using BCR-ABL transcript levels and measured by realtime quantitative polymerase chain reaction(RQ-PCR). Early molecular response is defined as a ratio BCR-ABL/ABL ≤10% on the international scale (IS).
Time frame: 3 months
Major molecular response(MMR) rate at month 3,6,9 and 12
Major molecular response is defined as a ratio BCR-ABL/ABL ≤0.1% on the international scale as measured by RQ-PCR.
Time frame: 3, 6, 9 and 12 months
MR4.0 rate at month 3,6,9 and 12
MR4.0 is defined as BCR-ABL/ABL ≤0.01% on the international scale.
Time frame: 3, 6, 9 and 12 months
MR4.5 rate at month 3,6,9 and 12
MR4.5 is defined as BCR-ABL/ABL ≤0.0032% on the international scale.
Time frame: 3, 6, 9 and 12 months
Complete cytogenetic response(CCyR)rate at month 3,6,9 and 12
Cytogenetic response (CyR) is based on the prevalence of Ph+ cells in metaphase from bone marrow (BM) sample . CCyR is defined as 0% Ph+ metaphases in the bone marrow.
Time frame: 3, 6, 9 and 12 months
Complete hematologic response(CHR) rate at month 1,2,3,4,5,6,9 and 12
Hematologic response will be assessed by complete blood count (CBC) and physical examination at each visit. CHR is defined as all of the following present: 1. white blood cell(WBC) count \<10×109/L 2. Platelet count \<450 ×109/L 3. Peripheral blood basophils \<5% 4. No blasts and no promyelocytes in peripheral blood 5. \< 5% myelocytes plus metamyelocytes in peripheral blood 6. No evidence of extramedullary disease, including no splenomegaly or hepatomegaly
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Time frame: 1,2,3,4,5,6,9 and 12 months
Time to first MMR
Evaluate the time from the date of randomization to the date of first documented MMR during treatment.
Time frame: up to 36 months
Time to first CCyR
Evaluate the time from the date of randomization to the date of first documented CCyR during treatment.
Time frame: up to 36 months
Duration of MMR
Duration of MMR is defined as the time from the date of first documented MMR to the earliest date of loss of MMR.
Time frame: up to 36 months
Duration of CCyR
Duration of CCyR is defined as the time from the date of first documented CCyR to the earliest date of loss of CCyR.
Time frame: up to 36 months
Event-free survival (EFS)
EFS is defined as the time from the date of randomization to the earliest occurrence of the following events: death due to any cause ; loss of CHR ,loss of PCyR ;loss of CCyR ; discontinuation of study treatment due to AE or treatment failure ; progression to AP/BC
Time frame: up to 36 months
Progression-free survival (PFS)
PFS is defined as the time from the date of randomization to the earliest occurrence of progression to AP/BC or death from any cause.
Time frame: up to 36 months
Overall survival (OS)
OS is defined as the time from the date of randomization to the date of death from any cause.
Time frame: Frame:12 and 36 months
The incidence and severity of adverse events ((AE)
Assessed by number and severity of adverse events as recorded on the case report form NCI CTCAE v5.0.
Time frame: up to 36 months
Pharmacokinetics (PK) of HS-10096:Tmax
Serum concentrations of HS-10096 will be collected and analyzed to evaluate the PK of HS-10096.Tmax is the time to reach maximum (peak) plasma drug concentration after dose administration (hr).
Time frame: Up to approximately 36 months