A Study of Dasatinib as First-line Treatment for Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia (CML-CP)

Study Overview
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Brief Summary
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The purpose of this multicenter,open, prospective and single arm study is to evaluate the efficacy and safety of domestic dasatinib in the first-line treatment of newly diagnosed CML-CP.

Official Title
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Efficacy and Safety of Dasatinib in the First-line Treatment of Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia (CML-CP)

Conditions
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Chronic Myelogenous Leukemia - Chronic Phase

Intervention / Treatment
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* Drug: Dasatinib Tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥ 18 years and gender is not limited. The chronic-phased CML subjects with Ph + were definitely diagnosed within 6 months before the first use of the study drug. The diagnostic criteria refer to the 2016 edition of Chinese CML diagnosis and treatment guidelines. The Eastern Cooperative Oncology Group (ECOG) performance of 0-2. The function of main organs such as liver and kidney is normal, which shows that serum bilirubin is less than or equal to 1.5 × ULN； Serum ALT and AST ≤ 2.5 × ULN； Serum Cr ≤ 1.5 × ULN； Serum amylase and lipase ≤ 1.5 × ULN; Blood potassium, magnesium, phosphorus and total calcium were more than or equal to the lower limit of normal value, or were corrected to normal range before administration. The subjects voluntarily participate in and signed the informed consent form (ICF), and the process of signing the ICF meet the requirements of the Practice for quality management of drug clinical trials. Exclusion Criteria: Subjects who have received any TKI treatment in the past. Subjects who have received or are receiving anti CML chemotherapy drugs (except hydroxyurea). Subjects who have received major surgery or no recovery from previous surgery within 4 weeks (including 4 weeks) before the first use of the study drug. Subjects with mental illness, including epilepsy, dementia, severe depression, mania, etc. Subjects with a history of significant congenital or acquired hemorrhagic disease unrelated to CML. Disease history and comorbidities: a) uncontrolled severe disease or active infection that impairs the subject's ability to receive the treatment; b) Uncontrolled or major cardiovascular disease; c) Pulmonary hypertension; d) Subjects with pleural effusion or pericardial effusion of any grade are excluded when screening; when entering the study, subjects with remission of pleural / pericardial effusion of any grade previously diagnosed were allowed to participate in the study. Subjects with gastrointestinal dysfunction or gastrointestinal diseases that may significantly affect the absorption of the test drug, such as ulcers, uncontrollable nausea, vomiting, diarrhea, malabsorption syndrome, after a small bowel resection, etc. Cardiac dysfunction, including: a) complete left bundle branch block; b) Long QT syndrome, or known family history of long QT syndrome; c) Ventricular or atrial tachyarrhythmia of clinical significance; d) Clinically significant resting bradycardia (< 50 beats per minute); e) QTc>450msec； f) History of clinically confirmed myocardial infarction in the past 12 months; g) History of unstable angina in the past 12 months; h) Other clinicallysignificant heart diseases (e.g., congestive heart failure, etc.). Combined with other primary malignant tumors (except basal cell carcinoma of skin). Subjects who are receiving treatment with strong CYP3A4 inhibitors (e.g., erythromycin Ethylsuccinate, ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir, imipradil, etc.) and cannot discontinue or switch to other drugs before starting the study drug. Subjects who are receiving strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampicin, rifabutin, rifapentine, phenobarbital, Hypericum perforatum, etc.) and the treatment cannot be stopped or replaced by other drugs before starting the study drug. Subjectswho are receiving the treatment of drugs that may prolong QT interval, and the treatment can not be stopped or replaced by other drugs before starting to use the study drug. Previous history of acute (within 1 year before inclusion) or chronic pancreatitis. Known or suspected to be allergic to this kind of drug. Female and male subjects of childbearing age who cannot use adequate methods of contraception , including pregnant or lactating women. Subjects who are receiving the treatment of other test drugs or participated in the clinical trial of other drugs within one month. -

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dasatinib tablets<br>Dasatinib tablets 100 mg orally once daily | Drug: Dasatinib Tablets<br>* Tyrosine Kinase Inhibitor (TKI)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects who achieve and maintain major molecular response (MMR) at 12 months | MMR is defined as BCR-ABL1IS ≤ 0.1% | up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects who achieve and maintain MMR at 3，6 and 18 months | MMR is defined as BCR-ABL1IS ≤ 0.1% | up to 18 months | 
| Time to MMR Overall | The time to MMR for all participants is defined as the time from first use of the study drug until measurement criteria are first met for MMR. | up to 24 months | 
| Cumulative MMR rates at 6, 12 and 24 months | MMR is defined as BCR-ABL1IS ≤ 0.1% | up to 24 months | 
| Proportion of subjects who achieve and maintain MR4.0 and MR4.5 at 6, 12 and 24 months | MR4.0 is defined as BCR-ABL1IS ≤ 0.01%, MR4.5 is defined as BCR-ABL1IS ≤ 0.0032% | up to 24 months | 
| Cumulative complete cytogenic response (CCyR) rates at 12 and 24 months | CCyR is defined as 0% Ph+ metaphases | up to 24 months | 
| Proportion of subjects who achieve and maintain complete hematological response (CHR) at 3 months | CHR was defined as peripheral blood WBC < 10x109 / L, PLT < 450x109 / L, no immature granulocytes, basophils < 0.05, no symptoms and signs of CML, spleen untouchable | up to 3 months | 
| Time to accelerated phase (AP ) / blast crisis (BC) | Time to AP / BC is defined as the time from the first use of the study drug to the date of CML related death or progression to AP or BC, whichever occurs first. For subjects without these events, the event was truncated at the date of the last evaluation (Hematology, extramedullary disease, or cytogenetic evaluation) | up to 24 months | 
| Progression-free Survival (PFS) | PFS is defined as the time from the first use of the study drug to the earliest occurrence of the following events: death from any cause (if death was the main cause of discontinuation) or progression to AP or BC. | up to 24 months | 
| Event free survival (EFS) | EFS is defined as the time from the first use of the study drug to the earliest occurrence of the following events during the study treatment: loss of CHR, loss of PCyCR, loss of CCyR, death from any cause during the treatment, and progression to AP or BC | up to 24 months | 
| ABL mutation rate after 6 months of treatment | The proportion of ABL mutations in subjects with BCR-ABL1IS > 1% or disease progression after 6 months of treatment | up to 6 months | 
| Incidence of adverse events (AEs) and serious adverse events (SAEs) to dasatinib | Evaluation of AEs, SAEs, and clinically relevant changes in laboratory tests according to laboratory reference ranges | up to 24 months |