Dasatinib Therapy Aiming for TFR in Patients with CML-CP

JRCT ID: jRCTs031180332

Registered date:18/03/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: chronic myeloid leukemia in chronic phase
• Date of first enrollment: 15/06/2016
• Target sample size: 300
• Study type: Interventional

Intervention(s)

The basic treatment in the induction phase is to administer 100 mg of dasatinib, once daily repeatedly. The maximum daily dose is 140 mg, and the dose can be increased, reduced or treatment be stopped at the discretion of investigators as needed. The dosage and administration should comply with the package insert approved in Japan. Treatment can be given both on an in-patient or out-patient basis.
When patients achieve MR4.5 during the induction phase for up to two years, patients will immediately enter into the consolidation phase. Then, they will be treated with dasatinib for one year in the consolidation phase. The starting dose of dasatinib in the consolidation is same dose as in the induction phase. The dose can be increased, reduced or treatment be stopped at the discretion of investigators as needed.
Sustained MR4.5 in the consolidation phase is defined as that MR4.5 is confirmed 5 consecutive times in BCR-ABL1 mRNA by RQ-PCR. However, if MR4.5 achieved 24 months or later after treatment start is lost, it is defined as that MR4.5 is not sustained, and follow-up period is completed.
If patients sustain MR.4.5 in the consolidation phase, patients will enter into the stop phase, and dasatinib will be stopped. If molecular relapse occurs in the stop phase, dasatinib treatment will be resumed at the final dose in the consolidation phase. The dose can be increased, decreased, and treatment can be stopped at the discretion of investigators as needed. Molecular relapse is defined as that loss of MMR is confirmed once or loss of MR4 is confirmed 2 consecutive times.

Outcome(s)

Primary Outcome

Percentage of patients in TFR who show no molecular relapse and do not need
resumption of dasatinib treatment 12 months after discontinuation of dasatinib treatment

Secondary Outcome

Percentage of patients in TFR 24, 36, and 48 months after discontinuation of dasatinib treatment.
Molecular relapse free survival 12 months after discontinuation of dasatinib treatment
Overall survival (OS) including all causes of death 12, 24, 36, and 48 months after discontinuation of dasatinib treatment
Dasatinib doses and time to MR4.5
Event free survival (EFS) during dasatinib treatment period.
Frequency and degree of TKI withdrawal syndrome after discontinuation of dasatinib treatment.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Induction phase
1) Patients with newly diagnosed CML-CP
2) Patients aged 18 years and over
3) Patients with ECOG performance status groups of 0 to 2
4) Patients with adequate functions of major organs (liver, kidney, and lung) (according to reference levels of each institution)
5) Patients who gave a written informed consent to participation in the trial. Minors who gave a written informed consent or one obtained from their legal representatives
Consolidation phase
Patients who achieved MR4.5 with dasatinib treatment in the induction phase
Stop phase
Patients who sustained MR4.5 for 12 months with dasatinib treatment in the consolidation phase

Exclude criteria

1)Active multiple cancers
2)Pregnant women and lactating mothers
3)Women who do not intend to or cannot use appropriate contraceptives during the registration period
4)Patients with a history or complications of the following severe or uncontrollable symptoms
-Myocardial infarction within the past 6 months
-Angina pectoris within the past 3 months
-Gastrointestinal haemorrhage within the past 3 months
-Congestive cardiac failure within the past 3 months
-Having plural effusion
-Electrocardiogram QTc interval prolonged exceeding 450 msec at the start of treatment (baseline) (Fridericia correction)
-Present or past history of pulmonary hypertension
5)Patients with a history or complications of diseases judged as inappropriate for study implementation by investigators.

Related Information

• Primary Sponsor: Yoshida Chikashi
• Source(s) of Monetary Support: Bristol-Myers Squibb Company
• Secondary ID(s): UMIN000022254