BOsutinib Gradual Increase trial

JRCT ID: jRCTs071180012

Registered date:16/01/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: chronic myeloid leukemia
• Date of first enrollment: 16/01/2019
• Target sample size: 35
• Study type: Interventional

Intervention(s)

Bostinib is given 200 mg once daily QD as the initial dose, and when the adverse event is grade 2 or less, it is increased by 100 mg per day every 2 weeks.
If the adverse event is grade 3 or higher, take a drug withdrawal until it falls below grade 1.
If an adverse event appears at 300 mg QD or more, the treatment with 100 mg reduced from the dose at which the adverse event reached grade 1 or less is resumed.
If an adverse event appears with 200 mg QD, the treatment resumes when the adverse event grade 1 or less is reached, and if it can maintain grade 2 or less, increase by 100 mg / day every 2 weeks.
If the same adverse event of grade 3 or more appears again when the dose is increased to the dose before the dose reduction, treatment is continued with the amount being 100 mg of that amount subtracted.
The above dose escalation continues until the daily dosage reaches 500 mg or until the protocol discontinuation criteria are met.

Outcome(s)

• Primary Outcome: Treatment drop-out rate due to AEs by 12 months after initiation of bosutinib

Secondary Outcome

1.Rate of treatment interruptions.
2.Mean bosutinib doses at 12 months after initiation of bosutinib.
3.Administration period of bosutinib and its median dose intensity/relative dose intensity up to 12 months after initiation of bosutinib.
4.Cumulative complete cytogenetic response (CCyR) maintenance rate at 6 and 12 months after initiation of bosutinib.
5.Cumulative major molecular response (MMR) rate and cumulative deep molecular response (DMR rate) at 3, 6, 9 and 12 months after initiation of bosutinib.
6.Incidence of all grades or grade 3 or 4 AEs
7.Peripheral blood lymphocyte profiling.
8.Bosutinib trough concentration, AEs and molecular responses.

Key inclusion & exclusion criteria

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

Include criteria

1) Major BCR-ABL-positive patients with chronic myelogenous leukemia
2) Patients aged 18 years or older at the time of registration
3) Patients who are resistant or intolerant to one or more other TKIs
4) ECOG performance status 0-2 patients
5) Patients whose major organs (liver, kidney, lung) function are maintained (standard values of each medical institution)
6) Patients with written consent (in the case of minors, parental consent is required)

Exclude criteria

1.Patients who have history of taking anti-cancer drugs other than hydroxyurea for CML.
2.Patients who are newly diagnosed CML.
3.Patients who have progress to AP or BP.
4.Patients with severe or uncontrollable complications.
5.Patients with complications of inflammatory bowel disease.
6.Pregnant and breastfeeding women, patients who wish to get pregnant within 12 months.
7.Patients who are participating in another clinical trial.
8.Patients with known T315I or V299L mutation.
9.Concomitant medications known to be strong inducers or inhibitors of P450 isoenzyme CYP3A4.
10.Known HIV and/or active viral hepatitis (hepatitis B or C).
11.Impaired cardiac function, including any of the following:
a. History of or presence of complete left bundle branch block, right bundle branch block plus left anterior hemiblock, bifascicular block in screening ECG.
b. ST depression of >1mm in 2 or more leads and/or T wave inversions in 2 or more contiguous leads in screening ECG.
c. Congenital long QT syndrome.
d. QTc > 450 msec in the screening ECG.
e. QT-prolonging concomitant medication.
f. History of or presence of significant ventricular or atrial tachyarrhythmias in screening ECG.
g. Myocardial infarction within 6 months prior to inclusion.
h. Unstable angina diagnosed or treated during the past 12 months.
i. uncontrolled hypertension, history of labile hypertension.

Related Information

• Primary Sponsor: Kimura Shinya
• Source(s) of Monetary Support: Pfizer
• Secondary ID(s): UMIN000032282