Clinical trial NCT04925141: A Study of Dasatinib as First-line Treatment for Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia (CML-CP)
Official title: Efficacy and Safety of Dasatinib in the First-line Treatment of Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia (CML-CP)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Myelogenous Leukemia - Chronic Phase
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-06-14
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Aged ≥ 18 years and gender is not limited.
2. 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.
3. The Eastern Cooperative Oncology Group (ECOG) performance of 0-2.
4. 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.
5. 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:

1. Subjects who have received any TKI treatment in the past.
2. Subjects who have received or are receiving anti CML chemotherapy drugs (except hydroxyurea).
3. 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.
4. Subjects with mental illness, including epilepsy, dementia, severe depression, mania, etc.
5. Subjects with a history of significant congenital or acquired hemorrhagic disease unrelated to CML.
6. 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.
7. 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.
8. 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.).
9. Combined with other primary malignant tumors (except basal cell carcinoma of skin).
10. 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.
11. 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.
12. 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.
13. Previous history of acute (within 1 year before inclusion) or chronic pancreatitis.
14. Known or suspected to be allergic to this kind of drug.
15. Female and male subjects of childbearing age who cannot use adequate methods of contraception , including pregnant or lactating women.
16. Subjects who are receiving the treatment of other test drugs or participated in the clinical trial of other drugs within one month.

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Primary outcomes:
measure: Proportion of subjects who achieve and maintain major molecular response (MMR) at 12 months
timeFrame: up to 12 months
Secondary outcomes:
measure: Proportion of subjects who achieve and maintain MMR at 3，6 and 18 months
timeFrame: up to 18 months
measure: Time to MMR Overall
timeFrame: up to 24 months
measure: Cumulative MMR rates at 6, 12 and 24 months
timeFrame: up to 24 months
measure: Proportion of subjects who achieve and maintain MR4.0 and MR4.5 at 6, 12 and 24 months
timeFrame: up to 24 months
measure: Cumulative complete cytogenic response (CCyR) rates at 12 and 24 months
timeFrame: up to 24 months
measure: Proportion of subjects who achieve and maintain complete hematological response (CHR) at 3 months
timeFrame: up to 3 months
measure: Time to accelerated phase (AP ) / blast crisis (BC)
timeFrame: up to 24 months
measure: Progression-free Survival (PFS)
timeFrame: up to 24 months
measure: Event free survival (EFS)
timeFrame: up to 24 months
measure: ABL mutation rate after 6 months of treatment
timeFrame: up to 6 months
measure: Incidence of adverse events (AEs) and serious adverse events (SAEs) to dasatinib
timeFrame: up to 24 months
Other outcomes:
Locations:
city: Shenzhen
country: China
facility: The Second People's Hospital of Shenzhen
state: Guangdong
city: Wuhan
country: China
facility: Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Shanghai
country: China
facility: Affiliated Zhongshan Hospital of Fudan University
state: Shanghai
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Medical College , Zhejiang University
state: Zhejiang
Study officials:
References: