Phase II study of dasatinib and ponatinib switched by molecular response in newly diagnosed BCR-ABL1-positive acute lymphoblastic leukemia

JRCT ID: jRCTs041190096

Registered date:13/12/2019

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: B-lymphoblastic leukemia/lymphoma with t(9;22)(q34;q11.2):BCR-ABL1
• Date of first enrollment: 16/01/2020
• Target sample size: 90
• Study type: Interventional

Intervention(s)

1. Induction including dasatinib and prednisolone
2. After intensified consolidation, dasatinib switches to ponatinib if pooe molecular response
3. Two types of consolidation (total 8 courses) and 12 courses maintenance with dasatinib or ponatinib by
molecular response
4. For patients who receive HCST, HSCT is carried out after consolidation1-1.

Outcome(s)

• Primary Outcome: 3-year event-free survival rate

Secondary Outcome

# Adverse event rate, serious adverse event rate,
# Complete hematological remission rate
# Molecular response
# complete molecular response rate
# 3-year overall survival rate
# 3-year relapse-free survival rate
# Molecular response, complete molecular response rate, 3-year overall survival rate, 3-year event-free survival rate and 3-year relapse-free survival rate in cases treated with ponatinib

Key inclusion & exclusion criteria

• Age minimum: >= 15age old
• Age maximum: < 65age old
• Gender: Both

Include criteria

1) Patients diagnosed with B-lymphoblastic leukemia / lymphoma with BCR-ABL1 (B-lymphoblastic leukemia / lymphoma with t (9; 22) (q34; q11.2): BCR-ABL1 in WHO classification revision 4th edition (2017)
2) BCR-ABL1 fusion gene positive.
(1) The BCR-ABL1 fusion gene is positive by chimeric gene screening.
(2) If the above 1) and 2) (1) are satisfied, the patient is diagnosed with Ph + ALL unless there is a clear record suggesting the existence of chronic phase. This is a rule that even if the major BCR-ABL1 fusion gene positive patient is BCR-ABL positive in neutrophil FISH, this test does not diagnose it as the first acute conversion case of chronic myelogenous leukemia.
3) Patients older than 15 and more and under 65 at the time of consent acquisition.
4) There is no prior treatment with this antineoplastic drug for this disease. If the administration period of prednisolone is less than one week before confirming that the BCR-ABL1 fusion gene is positive, it is not regarded as a prior treatment history. An intrathecal injection of methotrexate 12 mg/body within 1 week from the start date of prednisolone administration is not also considered to be a prior treatment history.
5) ECOG PS of 0, 1, 2, or 3.
6) Patients must have adequate cardiac, hepatic, renal, and pulmonary functions.
(1) No serious abnormalities of QTc prolongation (481 msec or more, equivalent to grade 2 or more) in the electrocardiogram.
(2) In cases echocardiography example, no LVEF less than 50% serious abnormalities are observed.
(3) The serum bilirubin level is 2.0 mg / dL or less.
(4) Serum creatinine level is 2.0 mg / dL or less.
(5) Percutaneous oxygen saturation concentration is 94% or more in room air.
7) Voluntary written consent must be given before enrollment.
8) The diagnosis has been notified to the patient.

Exclude criteria

1. Heart disease
(1) Uncontrolled angina, heart failure, myocardial infarction
(2) Congenital long QT syndrome
(3) Ventricular arrhythmia
2. Pulmonary fibrosis, interstitial pneumonia
3. Uncontrolled diabetes
4. Infection (Grade 4)
5. HIV (+)
6. HBsAg (+)
7. Complications increasing the frequency of adverse events of dasatinib
8. Complications increasing the frequency of adverse events of ponatinib
9. Obvious bleeding tendency
10. Mental disorders
11. Active double cancer
12. Pregnant and lactating woman
13. The principal investigator or co-investigator decision

Related Information

• Primary Sponsor: Dobashi Nobuaki
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development,Ministry of Health, Labour and Welfare