A Double-blind , Randomized, Multicenter, Phase 4 Study to Evaluate Efficacy and Safety of Oral Flumatinib 400mg Versus 600mg in Patients With Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase.
Overview
- Phase
- Phase 4
- Intervention
- Flumatinib mesylate tablets (400mg)
- Conditions
- CML, Chronic Phase
- Sponsor
- Jiangsu Hansoh Pharmaceutical Co., Ltd.
- Enrollment
- 200
- Locations
- 1
- Primary Endpoint
- Early molecular response(EMR) rate at 3 months
- Status
- Recruiting
- Last Updated
- 4 years ago
Overview
Brief Summary
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).
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed informed consent form.
- •Men or women aged more than or equal to (≥) 18 years, and less than (\<) 75 years.
- •ECOG performance status of 0-
- •Patients with philadelphia chromosome positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) within 6 months of diagnosis.
- •Adequate organ function.
- •Men or women should be using adequate contraceptive measures throughout the study; Females should not be breastfeeding at the time of screening, during the study and until 6 months after completion of the study.
- •Females must have evidence of non-childbearing potential.
Exclusion Criteria
- •Known atypical CML or presence of additional chromosomal abnormalities.
- •Known presence of the T315I mutation.
- •Treatment with tyrosine kinase inhibitor(s) prior to randomization.
- •Any treatment with anti-CML activity for longer than 2 weeks(exception of hydroxyurea or anagrelide) or hematopoietic stem cell transplantation prior to randomization .
- •Prior treatment with splenectomy.
- •Impaired cardiac function including any one of the following:
- •Resting corrected QT interval (QTc) \> 470 ms obtained from electrocardiogram (ECG), using the screening clinic's ECG machine and Fridericia's formula for QT interval correction (QTcF).
- •Any clinically important abnormalities in rhythm, conduction, or morphology of the resting ECG.
- •Any factors that increase the risk of QTc prolongation or risk of arrhythmic events,
- •Left ventricular ejection fraction (LVEF) ≤ 50%.
Arms & Interventions
Flumatinib (400mg)
Flumatinib 400mg QD
Intervention: Flumatinib mesylate tablets (400mg)
Flumatinib (600mg)
Flumatinib 600mg QD
Intervention: Flumatinib mesylate tablets (600mg)
Outcomes
Primary Outcomes
Early molecular response(EMR) rate at 3 months
Time Frame: 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).
Secondary Outcomes
- MR4.0 rate at month 3,6,9 and 12(3, 6, 9 and 12 months)
- Complete hematologic response(CHR) rate at month 1,2,3,4,5,6,9 and 12(1,2,3,4,5,6,9 and 12 months)
- Time to first MMR(up to 36 months)
- Event-free survival (EFS)(up to 36 months)
- Duration of CCyR(up to 36 months)
- Major molecular response(MMR) rate at month 3,6,9 and 12(3, 6, 9 and 12 months)
- Time to first CCyR(up to 36 months)
- Progression-free survival (PFS)(up to 36 months)
- MR4.5 rate at month 3,6,9 and 12(3, 6, 9 and 12 months)
- Complete cytogenetic response（CCyR）rate at month 3,6,9 and 12(3, 6, 9 and 12 months)
- Duration of MMR(up to 36 months)
- Overall survival (OS)(Frame:12 and 36 months)
- Pharmacokinetics (PK) of HS-10096：Tmax(Up to approximately 36 months)
- The incidence and severity of adverse events ((AE)(up to 36 months)