Nilotinib-Chemotherapy in CML Myeloid BP or Bcr-abl(+) AML (NICE-BORA)

This is an interventional treatment trial for Chronic Myeloid Leukemia in Myeloid Blast Crisis focused on measuring chronic myeloid leukemia, myeloid blastic phase, bcr-abl(+) acute myeloid leukemia, nilotinib Read More

Inclusion Criteria:

• Patients with previously-untreated patients having bcr-abl gene rearrangement (or t(9;22)) and 20% or more of myeloid blasts in bone marrow and/or blood, or converted CML CP/AP to MBP after initial imatinib treatment.
• 15 years old or older, but 65 years or younger
• Adequate performance status (Karnofsky score of 50 or more)
• Adequate hepatic and renal function (AST, ALT, bilirubin and creatinine < 2.5 x upper normal limit). Elevation of AST or ALT due to hepatic infiltration of leukemic cells will be permitted.
• Adequate cardiac function (left ventricular ejection fraction of 45% or more on heart scan or echocardiogram)
• Signed and dated informed consent must be obtained.

Exclusion Criteria:

• Patients without bcr-abl gene rearrangement
• Acute lymphoblastic leukemia with bcr-abl gene rearrangement or t(9;22)
• Any previous history of TKIs except for imatinib in CML CP.
• Therapy-related leukemia or leukemia after myelodysplastic syndrome.
• Patients with CNS leukemia
• Patients with primary granulocytic sarcoma without bone marrow involvement
• Prior chemotherapy for leukemia or anthracycline treatment for any malignancy. Hydroxyurea for reduction of leukemic cell burden before induction chemotherapy will be permitted.
• Presence of significant active infection
• Presence of uncontrolled bleeding
• Significant cardiovascular disease including myocardial infarction within previous 6 months
• Cardiac dysfunction: LVEF < 45% or institutional lower normal range (any higher value of them) by echocardiogram or MUGA scan; Long QT syndrome or its family history; Clinically significant resting bradycardia (<50 beats/minute); QTc > 450 msec (by QTcF formula) on baseline ECG . If QTcF > 450 msec and electrolytes are abnormal, retest QTc after the correction of electrolytes; Myocardial infarction within 12 months; Other clinically significant cardiac diseases (for example, unstable angina, congestive heart failure, uncontrolled hypertension or uncontrolled arrhythmia)
• Chronic or acute hepatic disease, pancreatic disease or severe renal disease
• Severe or life-threatening other medical conditions
• Any coexisting major illness or organ failure
• Patients with psychiatric disorder or mental deficiency severe as to make compliance with the treatment unlike, and making informed consent impossible History of congenital or acquired coagulopathy unrelated to malignancy
• Pregnancy issues: (a) pregnant woman, (b) lactating woman, (c) reproductive woman who does not confirm negative baseline pregnancy test (d) man or reproductive woman who cannot continue an appropriate contraceptive method (postmenopausal woman who has no menstruation for last 12 months is considered as non-reproductive)
• Patients with a diagnosis of prior malignancy unless disease-free for at least 5 years following therapy with curative intent (except curatively treated nonmelanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia)
• History of non-compliance or patient who cannot sign informed consent
• Hypersensitivity to nilotinib or any of the experience
• Concurrent medications (Gastrointestinal dysfunction that can significantly change the absorption of test drug; - Strong CYP3A4 inhibitor and cannot stop or change the medication before starting study; Medication to prolong QT interval and cannot stop or change the medication before starting study) • The capsules contain lactose, and nilotinib is therefore not recommended for patients with rare hereditary problems of galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption