Study to Evaluate Nilotinib in Chronic Myelogenous Leukemia (CML) Patients With SubOptimal Response

Study Overview
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Brief Summary
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To evaluate the major molecular response (MMR) rate at 12 months of nilotinib treatment on study in patients with Philadelphia Chromosome Positive (Ph+) chronic myelogenous leukemia in chronic phase (CML-CP) who have a suboptimal molecular response to imatinib at 18 months or later.

Official Title
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A Phase IV Study of Nilotinib in Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) Who Have Suboptimal Molecular Response on Imatinib

Conditions
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Philadelphia Chromosome Positive, Chronic Myelogenous Leukemia in Chronic Phase

Intervention / Treatment
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* Drug: Nilotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients ≥ 18 years of age. ECOG 0, 1, or 2. Have been diagnosed with Ph+ CML-CP and receiving imatinib therapy. Patients with suboptimal molecular response to imatinib treatment continued for at least 18 months (first line therapy) Suboptimal molecular response defined as all of the following conditions: Patients who have achieved CCyR (0% Ph+ chromosomes). Patients who don't achieve MMR (MMR defined as BCR-ABL/ABL ratio of ≤ 0.1% on the International Scale as detected by RQ-PCR). The treatment with imatinib defined as: Dose of 300 mg or higher daily must be maintained for a minimum of 3 months prior to study entry. Patients who meet the following laboratory tests criteria: total bilirubin < 1.5 x ULN, SGOT and SGPT < 2.5 x ULN, creatinine < 1.5 x ULN, Serum amylase and lipase ≤ 1.5 x ULN, Alkaline phosphatase ≤ 2.5 x ULN unless considered tumor related. Serum potassium, phosphorus, magnesium and calcium ≥ LLN or correctable with supplements prior to the first dose of study drug. Written informed consent prior to any study related screening procedures being performed. Exclusion Criteria: Prior accelerated phase or blast crisis CML. Previously documented T315I mutations. Presence of chromosomal abnormalities other than Ph+. Previous treatment with any other tyrosine kinase inhibitor except imatinib. Impaired cardiac function including any one of the following: Complete left bundle branch block Congenital long QT syndrome or family history of long QT syndrome History of or presence of significant ventricular or atrial tachyarrhythmias Clinically significant resting brachycardia (<50 bpm) QTcF > 450 msec on screening ECG Use of a ventricular-paced pacemaker Myocardial infarction during the last 12 months Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, unstable angina). Treatment with strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, St John's Wort), and the treatment cannot be discontinued or switched to a different medication prior to starting study drug. See Section 6.4.3 for complete list of these medications.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nilotinib<br>400 mg BID | Drug: Nilotinib<br>* 400 mg BID<br>* Other names: AMN107;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MMR Rate at 12 Mos. of Nilotinib Treatment on Study in Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) Who Have a Suboptimal Molecular Response to Imatinib at 18 Months or Later. | MMR is defined as BCR-ABL ratio (%) on IS ≤ 0.1% (corresponds to ≥ 3 log reduction of BCR-ABL transcripts from standardized baseline value | 12 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MMR Rate at 24 Months of Nilotinib Treatment on Study in Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) | MMR is defined as BCR-ABL ratio (%) on IS ≤ 0.1% (corresponds to ≥ 3 log reduction of BCR-ABL transcripts from standardized baseline value | 24 months after treatment | 
| Time to First MMR of Nilotinib in Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) . | MMR is defined as BCR-ABL ratio (%) on IS ≤ 0.1% (corresponds to ≥ 3 log reduction of BCR-ABL transcripts from standardized baseline value | month 24 | 
| Duration of MMR of Nilotinib in Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) . | MMR is defined as BCR-ABL ratio (%) on IS ≤ 0.1% (corresponds to ≥ 3 log reduction of BCR-ABL transcripts from standardized baseline value | month 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic phase, Chronic myelogenous leukemia, CML, Philadelphia chromosome positive, Ph+, Nilotinib, CML-CP, Suboptimal molecular response