Dasatinib very low dose for elderly CML patients

JRCT ID: jRCTs071180047

Registered date:14/03/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: chronic-phase chronic myeloid leukemia
• Date of first enrollment: 12/04/2017
• Target sample size: 50
• Study type: Interventional

Intervention(s)

Once-daily oral administration of dasatinib will be started at the dose of 20 mg. The treatment effect will be evaluated according to the European LeukemiaNet recommendations (ELN2013) at 3, 6, 9 and 12 months after initiation of treatment. Since ELN2013 does not stipulate the standards for 9 months after initiation of treatment, the standards at 6 months after initiation of treatment will be followed.
1)Treatment will be continued without changing the dose in case the effect is evaluated as optimal response and all AEs are of grade 2 or milder.
2)The daily dose of dasatinib will be increased by 20 mg in case the effect is evaluated as Warning and all AEs are of grade 2 or milder. However, if the dose has been reduced because of AEs of grade 3 or severer, treatment will be continued at the same dose without increasing the dose.
3)The protocol treatment will be discontinued and more appropriate treatment will be provided at the discretion of the attending physician in case the effect is evaluated as Failure, including progression of the disease stage into the accelerated phase or acute phase.
4)Administration of dasatinib will be suspended in case hematological toxicity of grade 3 or severer (neutrophil count less than 1,000/micro L or platelet count less than50,000/micro L) or non-hematological toxicity of grade 3 or severer are observed during all treatment periods. Treatment will be resumed after recovery from toxicity by reducing the daily dose of dasatinib by 20 mg. In case dasatinib is administered at the daily dose of 20 mg, the frequency of administration will be reduced to alternate-day administration of 20 mg. In case the above AEs are observed even with alternate-day administration of dasatinib at 20 mg/day, the protocol treatment will be discontinued, and more appropriate treatment will be provided at the discretion of the attending physician.

Outcome(s)

• Primary Outcome: Major molecular response (MMR) achievement rate at 12 months after initiation of treatment

Secondary Outcome

[1] Deep molecular response (DMR: MR4, MR4.5) achievement rate at 12 months after initiation of treatment
[2] Incidences of AEs of all grades or grade 3 or 4
[3] Treatment discontinuation rate due to AEs after 12 months of treatment with the drug
[4] Treatment discontinuation rate due to progression of the disease condition or treatment failure (Failure) after 12 months of treatment
[5] Association of Sokal score, Hasford score, and EUTOS score with treatment effects
[6] Association of BCR-ABL1 halving time with treatment effects at 3 months after initiation of treatment
[7] Association of blood concentration of dasatinib with treatment effects and AEs
[8] Association of peripheral blood T and NK cell profiles with treatment effects and AEs

Key inclusion & exclusion criteria

• Age minimum: >= 70age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Newly diagnosed chronic-phase chronic myeloid leukemia (CP-CML). The European LeukemiaNet (ELN) will be followed when evaluating the disease stage .
2) Patients aged 70 years or older at the time fo enrollment
3) Patients with ECOG performance status of 0 to 2
4) Patients whose primary organ (liver, kidneys and lungs) functions are maintained (each institutional standard values)
5) Patients who have given written informed consent (approval of the guardian will be required in the case the subject is a minor)

Exclude criteria

1) Patients with a history of treatment with drugs (imatinib, nilotinib, dasatinib, and interferon) for CML. Patients who have received prior treatment with Hydrea within 4 weeks can be enrolled.
2) Patients with a history of the following significant or uncontrollable cardiovascular disorders or their complications
2.1) Patients with obvious pleural effusion
2.2) Patients with a history of myocardial infarction within 6 months
2.3) Patients with a history of angina pectoris within 3 months
2.4) Patients with a history of congestive cardiac failure within 3 months
2.5) Patients with suspected congenital QT prolongation syndrome
2.6) Patients with QTc interval prolongation by 500 msec or more on 12-lead ECG
3) Patients receiving treatment for malignant disorders other than CML
4) Patients with uncontrollable severe disease history or complications
5) Patients with a history of hypersensitivity to dasatinib
6) Other patients who are deemed to be ineligible for the study by the attending physician

Related Information

• Primary Sponsor: Kimura Shinya
• Source(s) of Monetary Support: Bristol-Myers Squibb Co. Ltd
• Secondary ID(s): UMIN000024548