A Study of the Efficacy and Safety of Flumatinib in Patients With Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase.

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.

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.

Inclusion Criteria:

1. Signed informed consent form.
2. Men or women aged more than or equal to (≥) 18 years, and less than (<) 75 years.
3. ECOG performance status of 0-2.
4. Patients with philadelphia chromosome positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) within 6 months of diagnosis.
5. Adequate organ function.
6. 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.
7. Females must have evidence of non-childbearing potential.

Exclusion Criteria:

1. Known atypical CML or presence of additional chromosomal abnormalities.

2. Known presence of the T315I mutation.

3. Treatment with tyrosine kinase inhibitor(s) prior to randomization.

4. Any treatment with anti-CML activity for longer than 2 weeks(exception of hydroxyurea or anagrelide) or hematopoietic stem cell transplantation prior to randomization .

5. Prior treatment with splenectomy.

6. Impaired cardiac function including any one of the following:

   1. 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).
   2. Any clinically important abnormalities in rhythm, conduction, or morphology of the resting ECG.
   3. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events,
   4. Left ventricular ejection fraction (LVEF) ≤ 50%.
   5. During screening period, ECG examination showed average heart rate <50 beats per minute.
   6. Myocardial infarction occurred within 12 months of randomization;
   7. Congestive heart failure occurred within 6 months of randomization;
   8. Uncontrollable angina.

7. Stroke or transient ischemic attack within 6 months of randomization.

8. Any severe or uncontrolled systemic diseases (i.e. uncontrolled hypertension or diabetes).

9. Clinically severe gastrointestinal dysfunction that may affect drug intake, transport or absorption.

10. The presence of active infectious diseases has been known prior to randomization

11. History of significant congenital or acquired bleeding disorders unrelated to CML

12. Inadequate other organ function.

13. History of other malignancies.

14. History of hypersensitivity to any active or inactive ingredient of flumatinib.

15. Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either discontinued.

16. Major surgery within 4 weeks of randomization.

17. Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 within 4 weeks of randomization.

18. Any disease or condition that, in the opinion of the investigator, would compromise the safety of the patient or interfere with study assessments.

19. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.