Stop dasatinib study (STDAST)

JRCT ID: jRCTs071180043

Registered date:14/03/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: chronic myeloid leukemia-chronic phase
• Date of first enrollment: 22/08/2012
• Target sample size: 100
• Study type: Interventional

Intervention(s)

In accordance with the approved dosage, 50 mg, 2 tablets of dasatinib are taken once daily (100 mg/day) for 2 years and dasatinib administration will be stopped at the point of 2 years if the patients maintain CMR and the progress will be followed up in that patients.
When the major molecular recurrence during follow up period is confirmed after stop of dasatinib administration, dasatinib administration is restarted. One hundred mg of dasatinib with the approval dose and dosage is administered once daily. In addition, the administration of dasatinib is continued from the restarting point to three years after the end of dasatinib treatment period. And the study treatment is discontinued if CMR is achieved again or BCR-ABL/ABL ratios increase in 2 consecutive points in BCR-ABL genetic test.

Outcome(s)

• Primary Outcome: CMR maintenance rate at 1 year after a stop of dasatinib administration in patient who have maintained CMR for 2 years in treatment of TKIs

Secondary Outcome

* CMR maintenance rate at 2 and 3 years ,and relapse free survival (RFS), event free survival (EFS) , progression free survival (PFS) and overall survival (OS) at 1, 2 and 3 years after a stop of dasatinib administration in patient who have maintained CMR for 2 years after a start of clinical study.
* Two year CMR maintenance rate of patients at 24 months after the start of the study.
* Relationship between the time to CMR or MMR achievement and CMR maintenance rate at 1, 2 and 3 year after the stop of dasatinib administration
* Search for predictive factor of a stop of dasatinib administration
* Relationship between CMR maintenance rate and the following factors
- age, sex, Sokal score
- treatment duration of TKIs
- total duration of BCR-ABL negative conversion to enrollment
- LGL incidence
- total treatment period and total dose of dasatinib
* CMR achievement rate after re-administration in recurrent patients after stop of dasatinib administration
* Safety
* Investigation of gene mutation and splicing mutation

Key inclusion & exclusion criteria

• Age minimum: >= 16age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) CML-CP patients under treatment of imatinib, nilotinib or dasatinib
2) Patients without blast phase or accelerated phase CML
3) No extramedullary leukemia except hepatomegalia and splenoma
4) Patients with Ph+ or wild type in myeloid cytogenetics
5) Patients for CMR within 3 months before enrollment (Amp-CML: <5 copies/assay or PCR <=0.0032%)
6) Age >=16 years
7) ECOG performance status of 0-2
8) Laboratory test as follows
1. Albumin: >= lower limits of normal (LLN)
2. Total bilirubin: <= 3x upper limits of normal(ULN)
3. AST & ALT: <= 3xULN
4. Creatinine: <= 3xULN
5. Potassium: >= LLN
6. Magnesium: >= LLN
9) No pleural effusion in chest X-ray
10) SpO2 >=94%
11) Patient in compliance with the prescribed visit schedule
12) Written informed consent from the patient

Exclude criteria

1) Patients who attend other clinical trial
2) BCR-ABL point mutation (T315I, F317L, V299L)
3) QTc interval prolongation (>450msec)
4) Patient who has clear pleural effusion
5) Patients who have the following cardiovascular dysfunction
1. Impossible to measure QT interval in ECG
2. Complete left bundle branch block
3. Internal pacemaker
4. Congenital QT prolongation syndrome or family history
5. Tachycardia
6. Bradycardia (<50bpm)
7. Myocardial infarction within 6 months
8. Angina pectoris within 3 months
9. Congestive heart failure within 3 months
10. Patient who have the complications of cardiovascular disorder
6) Active double cancer
7) Pregnant or breastfeeding woman
8) Patient who have complications with serious or poor control
9) Mental disorder
10) Cognitive dysfunction
11) Patient who judges the investigator to have difficulty in participation in study

Related Information

• Primary Sponsor: Akashi Koichi
• Source(s) of Monetary Support: Bristol-Myers Squibb Company
• Secondary ID(s): UMIN000008583