Health Condition 1: null- CANCER
Conditions
Interventions
Intervention1: Nilotinib: 800 mg daily orally for period of 2 years
Control Intervention1: Imatinib: 600 mg dayily orally for period of 2 years
Sponsors
Novartis HealthCare Private Limited
Eligibility
Inclusion criteria
Inclusion criteria: 2. ECOG Performance Status of 0, 1, or 2; 3. Diagnosis of Ph-positive CML in chronic phase (CP) at the start of therapy with imatinib 400mg defined as follows: 15% blasts in peripheral blood and bone marrow; 30% blasts plus promyelocytes in peripheral blood and bone marrow; 20% basophils in the peripheral blood; ≥100x 109/L (≥ 100,000/mm3) platelets; no evidence of extramedullary leukemia involvement, with the exception of hepatosplenomegaly; 4. Patients with a suboptimal cytogenetic response to 400 mg of imatinib, defined as follows (cytogenetic analysis to document suboptimal response must have been done within 6 weeks of randomization): o No cytogenetic response at ≥ 3 to 6 months (more than 95% Ph+ metaphases) o No partial cytogenetic response at ≥ 6 to 12 months of treatment (36% to 95% Ph+ metaphases on bone marrow); or o No complete cytogenetic response at ≥ 12 to 18 months of treatment (1% to 35% Ph+ metaphases on bone marrow); Bone marrow karyotyping (BMK) is required on a minimum of 20 metaphases. Confirmation of SoR by FISH is allowed if BMK is done outside the screening window up to 4 weeks. 5. Patients receiving 400mg/daily imatinib standard dose for at least 3 months and no more than 18 months; 6. No prior use of imatinib dose higher than 400 mg daily; 7. Previous use of IFN is allowed at a maximum of 90 days . There is no time limit if the reason for switch from IFN to imatinib was intolerance. 8. Female patients of childbearing potential must have a negative urine pregnancy test prior to randomization; 9. Adults must agree to use an acceptable method of contraception to avoid pregnancy for the duration of the study and for 3 months after the end of study; 10. The following laboratory result must be present: o Creatinine 2.0 X ULN o Total bilirubin 1.5 X ULN ( 3.0 X ULN if related to disease); o SGOT and SGPT 2.5 X ULN ( 5.0 X ULN if related to disease); o Serum lipase ≤1.5 X ULN; o Alkaline phosphatase ≤2.5 X ULN ( 5.0 X ULN if related to disease) o Serum potassium, phosphorus, magnesium and calcium ≥ LLN [lower limit of normality] or correctable with supplements prior to first dose of study drug; 11. Written informed consent prior to any study procedures being performed
Exclusion criteria
Exclusion criteria: 1. Prior accelerated phase including clonal evolution or blast crisis CML; 2. Prior therapy with imatinib in combination with any other drug; 3. More than 18 months of imatinib therapy; 4. Patients who started imatinib therapy more than 12 months after the date of the original diagnosis by bone marrow aspiration; 5. Patients receiving imatinib dose of 300 mg daily; 6. Previous treatment with any other tyrosine kinase inhibitor except Glivec 7. Patients with myelotoxicity Grade 2 at the time of randomization, 8. Previously documented T315I mutations; 9. Achieved prior PCyR or CCyR on imatinib therapy and lost that response before entering the study; 10. Impaired cardiac function including one of the following: o Long QT syndrome or family history of long QT syndrome o Clinically significant resting brachycardia (50 bpm) o QTcF 450 msec on screening ECG (using the QTcF formula). If QTc 450 and electrolytes are not with normal ranges, electrolytes should be corrected and then the patient rescreened for QTc to certify QTc 450 msec ; o Myocardial infarction within one year of the first dose of study drug; o Other clinically significant heart disease (e.g., congestive heart failure, uncontrolled hypertension, unstable angina, significant ventricular or atrial tachyarrhythmias) 11. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug; 12. Patients actively receiving therapy with strong CYP3A4 inhibitors and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug; 13. Patients who are currently receiving treatment with any medications 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; 14. History of previous acute pancreatitis within one year of study entry or medical history of chronic pancreatitis; 15. Known cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS involvement, lumbar puncture is not required). 16. Women who are pregnant, breast feeding or of a childbearing potential without a negative urine pregnancy test at screening. Male or female patients of childbearing potential unwilling to use effective contraceptive precautions throughout the trial. Post-menopausal women must be ammenorrheic for at least 12 months to be considered of non-childbearing potential; 17. Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention; 18. Patients with any other clinically significant medical or surgical condition which, according to investigators discretion, should preclude participation; 19. Use of investigational agent within 28 days prior to enrollment in the study or foreseen use of an investigational agent during the study; 20. Patients unwilling or unable to comply with the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Rate of CCyR (CCyR defined as 0 percentage Ph positive metaphases) at 6 monthsTimepoint: Rate of CCyR (CCyR defined as 0 percentage Ph positive metaphases) at 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Rate of a MMR (MMR is defined as BCR-ABL less than or equal to 0.1 percentage on international scale) at 12 months Safety profile of nilotinib and imatinib treatment armsTimepoint: 12 Months | — |
Countries
Argentina, Brazil, Chile, Colombia, Costa Rica, Guatemala, India, Mexico, Panama
Contacts
Public ContactDr Mahesh Suryavanshi
Novartis
Outcome results
None listed