Health Condition 1: C921- Chronic myeloid leukemia, BCR/ABL-positive
Conditions
Interventions
Intervention1: NILOTINIB: NILOTIINIB 150 MG TWICE DAILY FOR 3 MONTHS
Control Intervention1: IMATINIB: IMATINIB 400 MG ONCE DAILY FOR 3 MONTHS
Sponsors
All India Institute Of Medical Sciences Institute Grant
Eligibility
Inclusion criteria
Inclusion criteria: Male or female patients more than or equal to 18 years of age Patients with newly diagnosed Chronic Myeloid leukaemia in the CML-CP phase as diagnosed with Bone marrow aspiration or peripheral smear or Philadelphia chromosome Qualitative RT-PCR BCR-ABL Serum albumin Levels more than 3.5 gm per decilitre Patients who provide written informed consent prior to any study-related screening procedures being performed ECOG performance status up to 2 Serum creatinine less than1.5 mg or creatinine clearance more than or equal to 60 ml/min as per the Cockroft-Gault formula Serum bilirubin less than 1.5 Upper Normal Limit Serum AST and ALT less than three times Upper Normal Limit Able to understand the Patient information sheet and give informed consent Female patients of childbearing potential must have a negative serum pregnancy within seven days before initiation of the study drug Patients must have the following laboratory values Less than Lower Normal or corrected to within normal limits with supplements prior to the first dose of study medication Potassium more than Lower Limit Normal Magnesium more than Lower Limit Normal Phosphorus more than Lower Limit Normal Total calcium after correction for serum albumin more than LLN Documented Chronic phase CML will meet all the criteria defined by Less than 20% of basophils in peripheral blood Less than 10% of blasts in bone marrow BCR-ABL1 positive by cytogenetics or molecular study Does not meet any of the following diagnostic criteria for accelerated or blast phase No evidence of extramedullary leukemic involvement with the exception of hepatosplenomegaly
Exclusion criteria
Exclusion criteria: Patients who are not willing to participate and will not provide signed informed consent Uncontrolled DM that is defined as HbA1c more than 7.5 percent Serum total bilirubin more than 1.5 times Upper Limit Normal AST and ALT more than three times the Upper Limit Normal Serum Amylase and lipase more than 1.5 times the Upper Limit Normal Alkaline Phosphate more than 2.5 times the Upper Limit Normal unless considered tumour-related Patients in whom serum creatinine will be more than 1.6 mg per decilitre or creatinine clearance less than 60 ml per min Patients taking strong CYP2D6 and CYP3A4 inducers or inhibitors Patients taking drugs that are known to cause QT prolongation Clinically obvious active infection ECOG performance status 3 or 4 History of any gastric or malabsorption disorder or small bowel resection or gastric bypass surgery or uncontrolled nausea vomiting and diarrhoea or intestinal surgery Uncontrolled hypertension (systolic BP more than or equal to 160 mmHg or diastolic BP more than or equal to 95 mm Hg) Patients with pancreatic dysfunction or prior history of pancreatitis within one year of study Acute or chronic liver and pancreatic or severe renal disease is considered unrelated to the disease Administration of an investigational therapeutic agent within 30 days of day 1 Active psychiatric illnesses or social situations that would limit compliance with protocol requirements Use of therapeutic coumarin derivatives like warfarin or acenocoumarol History of significant congenital or acquired bleeding disorder unrelated to cancer Presence of Hepatitis B or HIVor Hep C Pregnant or lactating women or females of childbearing potential unwilling to use contraceptive precautions throughout the trial post-menopausal women must be amenorrhoeic for at least 12 months to be considered of non -childbearing potential Major surgery within 4 weeks prior to day 1 of study or who have not recovered from prior surgery Any medical treatment for CML prior to study entry for longer than 2 weeks with exception of hydroxyurea and or anagrelide Patients with another primary malignancy except if the other primary malignancy is neither currently clinically significant or requiring active intervention Impaired cardiac function including any one of the following Inability to determine QT interval on ECG LVEF less than 45 percent or below the institutional lower limit of the normal range as determined by echo Complete Left bundle branch block Use of a ventricular-paced pacemaker Congenital long QT syndrome or a known family history of long QT syndrome History of or presence of clinically significant ventricular or atrial tachyarrhythmias Clinically significant resting bradycardia less than 50 beats per minute QTc more than 450 msec on the baseline ECG as determined by central reading. If QTc is more than450 msec and electrolytes are not within normal ranges and electrolytes should be corrected and then the patient re-screened for QTc History of clinically documented myocardial infarction New York Heart Association Class II-IV heart disease History of unstable angina during the last 12 months
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To compare the efficacy of Low-dose Nilotinib versus Imatinib for attainment of Early Molecular response three months BCR-ABL IS ratio less than 10% in previously untreated newly Diagnosed CML Chronic phase PatientsTimepoint: 3 MONTHS | — |
Secondary
| Measure | Time frame |
|---|---|
| To calculate the proportion of patients who will achieve CHR at the end of three months of intervention To evaluate the safety profile of low-dose nilotinib arm and Imatinib in patients with cml in chronic phase CP patients To evaluate the number of patients who have relapsed or failed treatment during the course of intervention Adherence with therapy which is Self-reported Timepoint: 3 months | — |
Countries
India
Contacts
Public ContactDR RANJIT KUMAR SAHOO
AIIMS NEW DELHI
Outcome results
None listed