An Open Label, Randomized Study of Nilotinib vs. Standard Imatinib (400/600 mg QD) Comparing the Kinetics of Complete Molecular Response for CML-CP Patients with Evidence of Persistent Leukemia by RQ-PCR
- Conditions
- ilotinib vs. Standard Imatinib (400/600 mg QD) Comparing the Kinetics of Complete Molecular Response for CML-CP Patients with Evidence of Persistent Leukemia by RQ-PCRMedDRA version: 9.1Level: LLTClassification code 10009012Term: Chronic myelogenous leukemia
- Registration Number
- EUCTR2009-012616-40-GB
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 192
1. Patients =18 years old
2. Diagnosis of chronic myeloid leukemia in chronic phase (CML-CP) associated with BCR-ABL quantifiable by RQ-PCR (IS)
3. Documented CCyR* by bone marrow (standard cytogenetic test) or peripheral blood BCR-ABL<1% IS as defined in Appendix 1 of protocol
4. Persistent disease demonstrated by two PCR positive tests (ie., BCR-ABL level <1% IS) which have been performed during the past nine months and are at least 10 weeks apart. One of these should be performed within 3 months of randomization (see definition of persistent disease in Appendix 1).
5. Treatment with imatinib for at least 2 years with 400 mg or 600 mg and a stable dose (the dose has not changed in the previous 6 months.) Patients who received imatinib 800 mg/day in the past, but the dose was subsequently reduced to 600 mg or 400 mg/day more than 6 months before the randomization are also eligible for this study.
6. Must have been treated with Glivec®/Gleevec®
7. No other current or planned anti-leukemia therapies
8. ECOG Performance status 0,1, or 2
9. Adequate end-organ function as defined by:
a. Total bilirubin < 1.5 x ULN (ULN = upper limit of normal in a local institution lab). Does not apply to patients with isolated hyperbilirubinemia (e.g., Gilbert’s disease) grade <3.
b. AST (SGOT) and ALT (SGPT) < 2.5 x ULN
c. Serum amylase and lipase = 1.5 x ULN
d. Alkaline phosphatase = 2.5 x ULN
10. Patients must have the following laboratory values (WNL = within normal limits at the local institution lab) or corrected to within normal limits with supplements prior to the first dose of study medication
a. Potassium (WNL)
b. Magnesium (WNL)
c. Phosphorus (WNL)
d. Calcium (WNL)
11. Life expectancy of more than 12 months in the absence of any intervention
12. Patient has given written, informed consent to participate in the study
*Note: One of the PCR tests used to document persistent disease may also serve to document CCyR, if <1% on IS (see Inclusion criteria #4)
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
1. Prior accelerated phase or blast crisis
2. Patient has evidence of rising PCR (a confirmed >1 log increase in previous 6 months)
3. Patient has received another investigational agent within last 6 months or TKIs other than imatinib
4. Prior stem cell transplantation
5. Impaired cardiac function including any one of the following:
a. Inability to monitor the QT/QTc interval on ECG
b. Long QT syndrome or a known family history of long QT syndrome
c. Clinically significant resting brachycardia (<50 beats per minute)
d. QTc > 450 msec on baseline ECG (using the QTcF formula). If QTcF >450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patientre-screened for QTc
e. Myocardial infarction within 12 months prior to starting study
f. Other clinically significant uncontrolled heart disease (e.g. unstable angina, congestive heart failure or uncontrolled hypertension)
g. History of or presence of clinically significant ventricular or atrial tachyarrhythmias
6. Administration of cytokine therapy (e.g. G-CSF, GM-CSF or SCF) within 4 weeks prior to study entry
7. Atypical BCR-ABL transcript not quantifiable by standard RQ-PCR.
8. Another primary malignant disease, which requires systemic treatment (chemotherapy or radiation)
9. Acute liver disease
10. Acute or chronic pancreatic disease
11. Another severe and/or life-threatening medical disease
12. History of significant congenital or acquired bleeding disorder unrelated to cancer
13. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug
14. 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
15. 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
16. Patients who are: (a) pregnant, (b) breast feeding, (c) of childbearing potential without a negative pregnancy test prior to baseline and (d) male or female of childbearing potential unwilling to use contraceptive precautions throughout the trial (post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential)
17. Interruption of imatinib therapy for a cumulative period in excess of 21 days in the preceding 3 months
18. Major toxicity on imatinib in past 3 months
19. History of non-compliance or inability to grant informed consent
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: • To compare the rate of confirmed best cumulative CMR within the first year of study therapy with nilotinib or imatinib;Secondary Objective: • To characterize kinetics of CMR achieved in both treatment arms<br>• To compare progression-free survival between the two arms;Primary end point(s): Rate of confirmed best cumulative CMR within the first year of study therapy with nilotinib or imatinib
- Secondary Outcome Measures
Name Time Method