Overview

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

Status:
Unknown status
Trial end date:
2019-12-01
Target enrollment:
0
Participant gender:
All
Summary
The current standard therapy in previously untreated adults with chronic phase (CP) of CML is imatinib and the result of long-term follow-up of IRIS study proves that imatinib for CML CP is reasonable therapy.(1, 2) However, some patients were initially diagnosed as advanced CML, accelerated phase (AP) or blastic phase (BP). Various chemotherapies were tried and were found that there were no highly effective chemotherapies for CML BP.(3-11) Imatinib in patients with these advanced CML is also disappointing because of low response rates as well as short response duration, and sudden transformation to BC is found even in initial CML CP patients. (12-17). Recent studies showed that nilotinib or dasatinib is better than imatinib in terms of rapid response and higher molecular response in newly diagnosed CML patients.(18-21) More potent bcr-abl suppression of nilotinib is supposed to be more active than imatinib even in patients with advanced CML. However, nilotinib in patients with imatinib-resistant or -intolerant CML BP showed low hematologic response and major cytogenetic response.(22, 23)
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Ulsan University Hospital
Collaborator:
The Korean Society of Hematology CML working party
Treatments:
Cytarabine
Criteria
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