A clinical study which compares the benefit of optimizing the dose ofimatinib (Gleevec/Glivec) with Nilotinib (Tasigna) in patients with chronicmyelogenous leukemia who have not optimally responded to standardtreatment with Imatinib.

• Conditions: IMATINIB DOSE OPTIMIZATION COMPARED WITH NILOTINIB IN PATIENTS WITH CML AND SUBOPTIMAL RESPONSE TO STANDARD-DOSE IMATINIB; MedDRA version: 14.1Level: LLTClassification code 10009012Term: Chronic myelogenous leukemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2008-007054-35-DE
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-06-04
• Last Update Posted: 7 October 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 188

Inclusion Criteria

1.Male or female, aged = 18 years;
2.ECOG Performance Status of 0, 1, or 2 (see Appendix A);
3.Ph-positive CML in chronic phase (CP) at study enrollment is defined
as follows:
•<15% blasts in peripheral blood and bone marrow;
•<30% blasts plus promyelocytes in peripheral blood or 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):
•No cytogenetic response at = 3 to <6 months (more than 95% Ph+ metaphases)
•No partial cytogenetic response at = 6 to <12 months of treatment (and at least 36% to 95% Ph+ metaphases on bone marrow); or
•No complete cytogenetic response at = 12 to <18 months of treatment (and have at least 1% to 35% Ph+ metaphases on bone marrow);
•Bone marrow karyotyping (BMK) is required on a minimum of 20 metaphases; Confirmation of suboptimal response (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 but no longer than 18 months;
6.No prior use of imatinib dose higher than 400 mg daily;
7.Previous use of IFN, taken prior to imatinib treatment, 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 within 7 days prior to registration;
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 study termination;
10.The following laboratory result must be present:
•Creatinine <2.0 X ULN
•Total bilirubin <1.5 X ULN (< 3.0 X ULN if related to disease);
•SGOT and SGPT < 2.5 X ULN;
•Serum lipase =1.5 X ULN;
•Alkaline phosphatase =2.5 X ULN
•Serum potassium, phosphorus, magnesium and calcium = lower limit of normality (LLN) or corrected to within normal limits with supplements prior to first dose of study drug;

11.Written informed consent prior to any study procedures being performed (see Appendix C).

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

1. Prior accelerated phase including clonal evolution or blast crisis CML;
2. Prior therapy with imatinib in combination with any other CML drug other than Hydroxyurea and/or Anagrelide;
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
5. Unable to tolerate imatinib at standard dose (400mg);
6. Previous treatment with any other tyrosine kinase inhibitor except Glivec and/or CML therapy other than INF, hydroxyurea, and/or anagrelide
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:
• Long QT syndrome or family history of long QT syndrome
• Clinically significant resting brachycardia (<50 bpm)
• 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
• Myocardial infarction =12 months prior to the first dose of study drug;
• 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. 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 nonchildbearing 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.

Study & Design

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