A phase II multi-center, open-label, study of Nilotinib at a dose of 300mg twice daily in adult patients with newly diagnosed Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia in chronic phase (CML-CP) - ICORG 08-02

Phase 1

• Conditions: Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia in chronic phase (CML-CP); MedDRA version: 14.1Level: LLTClassification code 10009012Term: Chronic myelogenous leukemiaSystem Organ Class: 100000004864

• Registration Number: EUCTR2008-004551-30-IE
• Lead Sponsor: ICORG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-07-10
• Last Update Posted: 19 September 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

•Male or female patients = 18 years of age
•ECOG performance status 0, 1, or 2
•Patients with CML-CP 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. FISH cannot be used.
•Diagnosis of chronic myelogenous leukemia in chronic phase with cytogenetic confirmation of Philadelphia chromosome of (9;22) translocations in more than one metaphase to prove clonality (where possible a review of up to 20 metaphases is desirable to provide a more accurate assessment of baseline Ph+ chromosome positivity).
•Documented chronic phase CML will meet all the criteria defined by:
1. <15% blasts in peripheral blood and bone marrow
2. <30% blasts plus promyelocytes in peripheral blood and bone marrow,
3. <20% basophils in the peripheral blood,
4. =100 x 109/L (=100,000/mm3) platelets
5. No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly.
•Adequate end organ function as defined by:
1. total bilirubin <1.5xULN
2. AST and ALT <2.5xULN
3. estimated GFR of = 30 ml/min which may be less restrictive
4. Serum amylase and lipase =1.5xULN
5. Aklaline phosphatase = 2.5 xULN unless considered tumor related
•Female patients of childbearing potential must have a negative serum pregnancy test within 7 days before initiation of study drug
•Patients must have the following laboratory values (=(lower limit of normal) or corrected to within normal limits with supplements prior to the first dose of study medication:-
1.Potassium =LLN
2.Magnesium = LLN
3.Phosphorous = LLN
4.Total calcium, (corrected for serum albumin) = LLN
•Ability to provide written informed consent prior to any study related screening procedures being performed.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

•Patients who are considered Ph- because they do not have a confirmed cytogenetic diagnosis of Philadelphia Chromosome with (9,22) translocation
•Previously documented T315I mutations
•Any medical treatment for CML (including imatinib) prior to study entry for longer than 4 weeks with the exception of Hydroxyurea and/or Anagrelide
Impaired cardiac function including any one of the following:-
*LVEF<45% or below the institutional lower limit of the normal range (whichever is higher) as determined by echocardiogram
*Inability to determine the QT interval on ECG
*Complete left bundle branch block
*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 brachycardia (<50 beats per minute).
*QTc>450 msec on the average of three serial baseline ECG (using the QTcF formula). If QTcF>450msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-scanned for QTc.
*History of clinically documented myocardial infarction within past 12 months
*History of unstable angina (during the last 12 months)
*Other clinically significant heart disease (e.g. congestive heart failure or uncontrolled hypertension).
•Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection).
•History of significant congenital or acquired bleeding disorder unrelated to cancer.
•Major surgery within 4weeks prior to day-1 of study or who have not recovered from prior surgery.
•Treatment with other investigational agents within 30 days of Day-1.
•History of non-compliance to medical regimens or inability to grant consent
•Patients with other primary malignancy except if the other primary malignancy is neither currently clinically significant or requiring active intervention
•Patients actively receiving therapy with strong CYP3A4 inhibitors (e.g. erythromycin, ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir, mibefradil) and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug. See link for complete list of these medications: http://medicine.iupui.edu/flockhart/table.htn. The Principal Investigator must be contacted if a patient needs to be started on any of these drugs during study treatment.
•Patients actively receiving therapy with strong CYP3A4 inducers, (e.g. Dexamethasone, 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 of these medications: http://medicine.iupui.edu.flockhart/table.htm. The Principal Investigator must be contacted if a patient needs to be started on any of these drugs during study treatment.
•Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypass surgery).
•History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis.
•Acute or chronic liver, pancreatic or severe renal disease considered unrelated to CML
•Patients who are currently receiving treatment with any medications that have the pot

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified