Optimizing Chronic Myeloid Leukemia Treatment: A Randomized Phase II Trial of Upfront Low-Dose Nilotinib in the Indian Context
- Conditions
- Health Condition 1: C921- Chronic myeloid leukemia, BCR/ABL-positive
- Registration Number
- CTRI/2024/03/064707
- Lead Sponsor
- All India Institute Of Medical Sciences Institute Grant
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Yet Recruiting
- Sex
- Not specified
- Target Recruitment
- 0
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
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method To calculate the proportion of patients who will achieve CHR at the end of three months of intervention <br/ ><br> <br/ ><br>To evaluate the safety profile of low-dose nilotinib arm and Imatinib in patients with cml in chronic phase CP patients <br/ ><br> <br/ ><br>To evaluate the number of patients who have relapsed or failed treatment during the course of intervention <br/ ><br> <br/ ><br>Adherence with therapy which is Self-reported <br/ ><br>Timepoint: 3 months