Safety confirmation test of ponatinib against Philadelphia chromosome positive leukemia with relapse or refractory to children

JRCT ID: jRCTs041190048

Registered date:24/06/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Philadelphia chromosome positive leukemia
• Date of first enrollment: 19/11/2019
• Target sample size: 6
• Study type: Interventional
• Intervention(s): oral Ponatinib at a dose of 15~25 mg/m^2 for 28 days.

Outcome(s)

• Primary Outcome: FDT (Fixed dosed toxicity)

Secondary Outcome

1) Major hematologic response, cytogenetic response and molecular response after the treatment of ponatinib
2) Temporal change of minute residual lesions (Ig / TCR PCR MRD, FCM MRD, chimeric gene MRD) of ponatinib
3) Relation between BCR-ABL chimeric gene mutation and MRD disappearance rate / MRD recurrence rate
4) Pharmacokinetics of ponatinib
5) Relationship between ponatinib blood concentration and MRD elimination rate , MRD recurrence rate
6) Accomplishment rate of ponatinib treatment
7) Adverse Event Incidence

Key inclusion & exclusion criteria

• Age minimum: >= 3age old
• Age maximum: < 15age old
• Gender: Both

Include criteria

1) Diagnosis of CML that was resistant/intolerant to 2nd generation TKI, or of Ph+ALL that was relapsed/refractory or intolerant to 2nd generation TKI
2) Aged 3-14 years
3) BSA >=0.6 m2
4) ECOG PS score of 0-2.

Exclude criteria

1) Symptoms of central nervous system bleeding of Grade 3 or more according to the CTCAE v4.0.
2) Infection that is difficult to control
3) Females who are pregnant, breastfeeding or possibly pregnant.
4) Down syndrome
5) long QT
6) diabetes mellitus
7) hyperlipidemia
8) Total bilirubin: more than 3 times the upper limit of the reference value adjusted for age.
9) liver cirrhosis
10) severe psychiatric disorder
11) a history of ischemic cardiac disease
12) a history of thrombosis
13) Creatinine: more than 3 times the upper limit of the reference value adjusted for age.
14) a history of renal failure
15) a history of congenital or acquired immunodeficiency syndrome.
16) have not recovered (>Gr1 by CTCAE Ver 4.0) from adverse events due to previous agents with the exception of alopecia
17) have had cytotoxic chemotherapy, intrathecal therapy or radiotherapy within 14 days of starting ponatinib with the exception of other TKI, steroid or intrathecal therapy for diagnosis
18) have received imatinib within 5 days of starting ponatinib
19) have received dasatinib within 3 days of starting ponatinib
20) have received nilotinib within 8 days of starting ponatinib
21) have received bosutinib within 10 days of starting ponatinib
22) malabsorption syndrome
23) intestinal disease that effect on the absorption of ponatinib
24) uncontrolled cardiac disease
25) uncontrolled hypertension
26) hematopoietic stem cell transplant < 3 months prior to enrollment or any evidence of on-going GVHD
27) received any other agent causes long QT
28) second malingnancy other than CML or Ph+ALL
29) received surgical procedure within 14 days of starting ponatinib (with the exception of the insertion of CV catheter or bone marrow biopsy)
30) a history of HIV, HBV or HCV infections
31) lipase: more than 1.5 times the upper limit of the reference value.
32) amylase: more than 1.5 times the upper limit of the reference value

Related Information

• Primary Sponsor: Kodama Yuichi
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development,National Cancer Center Japan,National Cancer Center Japan