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

Sponsor

Chia Tai Tianqing Pharmaceutical Group Co., Ltd. (Industry)

Overall Status

Completed

CT.gov ID

NCT04925141

Collaborator

(none)

Enrollment

Locations

Arm

42.9

Actual Duration (Months)

15.5

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myelogenous Leukemia - Chronic Phase	Drug: Dasatinib Tablets	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

62 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

May 10, 2016

Actual Primary Completion Date :

Oct 22, 2018

Actual Study Completion Date :

Dec 6, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dasatinib tablets Dasatinib tablets 100 mg orally once daily	Drug: Dasatinib Tablets Tyrosine Kinase Inhibitor (TKI)

Arm

Intervention/Treatment

Experimental: Dasatinib tablets

Dasatinib tablets 100 mg orally once daily

Drug: Dasatinib Tablets

Tyrosine Kinase Inhibitor (TKI)

Outcome Measures

Primary Outcome Measures

Proportion of subjects who achieve and maintain major molecular response (MMR) at 12 months [up to 12 months]
MMR is defined as BCR-ABL1IS ≤ 0.1%

Secondary Outcome Measures

Proportion of subjects who achieve and maintain MMR at 3，6 and 18 months [up to 18 months]
MMR is defined as BCR-ABL1IS ≤ 0.1%
Time to MMR Overall [up to 24 months]
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.
Cumulative MMR rates at 6, 12 and 24 months [up to 24 months]
MMR is defined as BCR-ABL1IS ≤ 0.1%
Proportion of subjects who achieve and maintain MR4.0 and MR4.5 at 6, 12 and 24 months [up to 24 months]
MR4.0 is defined as BCR-ABL1IS ≤ 0.01%, MR4.5 is defined as BCR-ABL1IS ≤ 0.0032%
Cumulative complete cytogenic response (CCyR) rates at 12 and 24 months [up to 24 months]
CCyR is defined as 0% Ph+ metaphases
Proportion of subjects who achieve and maintain complete hematological response (CHR) at 3 months [up to 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
Time to accelerated phase (AP ) / blast crisis (BC) [up to 24 months]
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)
Progression-free Survival (PFS) [up to 24 months]
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.
Event free survival (EFS) [up to 24 months]
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
ABL mutation rate after 6 months of treatment [up to 6 months]
The proportion of ABL mutations in subjects with BCR-ABL1IS > 1% or disease progression after 6 months of treatment
Incidence of adverse events (AEs) and serious adverse events (SAEs) to dasatinib [up to 24 months]
Evaluation of AEs, SAEs, and clinically relevant changes in laboratory tests according to laboratory reference ranges

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Second People's Hospital of Shenzhen	Shenzhen	Guangdong	China	518035
2	Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei	China	430030
3	Affiliated Zhongshan Hospital of Fudan University	Shanghai	Shanghai	China	200032
4	The First Affiliated Hospital, Medical College , Zhejiang University	Hangzhou	Zhejiang	China	310013