Efficacy and safety evaluation of nilotinib as primary treatment in newly diagnosed Philadelphia chromosome positive(Ph+) chronic myeloid leukemia(CML) patients
- Conditions
- Diseases of the blood and blood -forming organs and certain disorders involving the immune mechanism
- Registration Number
- KCT0000615
- Lead Sponsor
- Seoul National University Hospital
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot yet recruiting
- Sex
- All
- Target Recruitment
- 114
1)Patients aged 18 years or more
2)Patients with Philadelphia chromosome positive(Ph+) chronic myeloid leukemia in chronic phase within 6 months of diagnosis (date of initial diagnosis is the date of first cytogenetic analysis. Standard conventional cytogenetic analysis must be done on bone marrow. Fluorescent In-situ Hybridization(FISH) is not allowed to be used.)
3)Diagnosis of Chronic Myeloid leukemia in Chronic Phase with cytogenetic confirmation for the presence of Philadelphia chromosome(cytogenetic analysis should be done on bone marrow in standard conventional method. Fluorescent In-situ Hybridization(FISH) is not allowed to be used.)
The chronic phase is defined when all of the following criteria are met:
- Blasts <15% in peripheral blood and bone marrow
- Sum of blasts and promyelocytes <30% in peripheral blood and bone marrow
- Basophils <20% in peripheral blood
- Platelet count =100x109/L (=100,000/mm3)
- No evidence of extramedullary leukemic involvement, except hepatomegaly and splenomegaly
4) Patients with Eastern Cooperative Oncology Group (ECOG) of 0~2
5) Patients with QTc<450msec on screening ECG
6) Patients with proper organ functions
- bilirubin < 1.5 x ULN
- creatinine < 1.5 x ULN
- Liver function test; AST(SGOT) and ALT(SGPT) < 2.5 x ULN
- alkaline phosphatase = 2.5 x ULN(only if it is not related to tumor)
- Serum amylase and lipase = 1.5 x ULN
7) Patients without any other activated malignant tumor
8) Women of childbearing potential must have a negative urine or serum pregnancy test within 14 days prior to starting administration of the investigational product .
9) Patients who have voluntarily written informed consent, or whose legal guardian given a written consent to participate in this clinical study
1)BCR-ABL positive chronic myeloid leukemia patients with negative Philadelphia chromosome
2)Patients who received bone marrow suppressive anti-cancer therapy excluding Hydroxyurea or Anagrelide
3)Patients who have been treated with a tyrosine kinase inhibitor or anti-leukemic agent, or Hematopoietic Stem Cell Transplantation (HSCT) for longer than 2 weeks
4)Patients with any cardiac dysfunctions stated below:
-Immeasurable QT intervals on screening ECG
-Complete left bundle branch block
-Using pacemaker
-Congenital or known family history of Long QT Syndrome(LQTS)
-History or presence of clinically significant ventricular or atrial tachyarrhythmias
-Clinically significant brachycardia at rest(<50 times per minute)
-QTcF =450msec in three consecutive baseline screening ECGs
-History of clinically confirmed myocardial infarction
-History of unstable angina pectoris(within past 12 months)
-Uncontrolled congestive heart failure or hypertension
5)Patients with cytopathologically identified CNS involvement (no need for lumbar puncture prior to the clinical study if there are no symptoms)
6)Patients who received radiotherapy on 25% or more of bone marrow for other malignant disease in the past
7)Use of therapeutic coumadin derivatives(that is, warfarin, acenocoumarol, phenprocoumon)
8)Severe or uncontrolled chronic medical condition(that is, uncontrolled diabetes, active infection or uncontrolled infection)
9)Medical history of congenital or acquired bleeding disorders not related to leukemia
10)Patients who have undergone major surgery = 2 weeks prior to starting study drug or who have not been recovered from side effects of such therapy
11)Patients with another primary malignancy that is currently clinically significant
12)Patients who are receiving therapy with strong CYP3A4 inhibitors(e.g.,erythromycin, ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir, mibefradil) or CYP3A4 inducers(e.g.,dexamthasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbitol, St.John's Wort), and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug (See link for complete list: http://medicine.iupui.edu/flockhart/table.htm.)
13)Patients who are currently receiving treatment with any medication that have the potential to prolong the QT interval, and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug (See link for complete list: http://www.torsades.org/medical-pros/drug-lists/printable-drug-list.cfm.)
14)Impaired gastrointestinal functions or gastrointestinal diseases that may alter the absorption of the study drug (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastrointestinal bypass)
15)History of acute pancreatitis or chronic pancreatitis in the past year
16)Other concurrent medical conditions such as acute or chronic liver, pancreas, or severe kidney diseases
17)Patients who are pregnant or breast feeding
18)Women of childbearing potential who have not received contraceptive operation (Post menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.) Women of childbearing potential must have a negative pregnancy test in order to participate in this study and must maintain an effective contraceptive measure during the study. Periodical abstinence(e.g.: calend
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Complete molecular response rate(CMR rate) after starting Nilotinib treatment
- Secondary Outcome Measures
Name Time Method Adverse event, clinical laboratory test(hematology, blood chemistry, urine test), vital signs(blood pressure, pulse, body temperature), physical examination