Phase II Nilotinib With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia (CML)
Condition: Leukemia, Myelogenous, Chronic
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase
Intervention: Nilotinib
Intervention description: 400 mg orally twice daily
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 148.0
Sex: All
Minimum age: 16 Years
Healthy volunteers: No
Keywords: Chronic phase CML; Newly diagnosed chronic phase CML; AMN107

Summary:

      The goal of this clinical research study is to learn if an experimental agent, AMN107
      (nilotinib), can help to control CML in chronic phase. The safety of this experimental agent
      will also be studied.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Diagnosis of Ph-positive or Bcr-positive CML in early chronic phase CML (i.e., time
             from diagnosis 12 months). Except for hydroxyurea, patients must have received no or
             minimal prior therapy, defined as <1 month (30 days) of prior interferon-alpha (with
             or without cytarabine) and/or an FDA-approved Tyrosine Kinase Inhibitor (TKI).
             Patients with de novo accelerated phase will be treated but analyzed separately.

          2. Age >/= 16 years (Age >18 years to participate in optional symptom burden assessment)

          3. Eastern Cooperative Oncology (ECOG) performance of 0-2.

          4. Adequate end organ function, defined as the following: total bilirubin < 1.5 x upper
             limit of normal (ULN), alanine aminotransferase (ALT/SGPT) < 2.5 x ULN, creatinine <
             1.5 x ULN.

          5. Patients must sign an informed consent indicating they are aware of the
             investigational nature of this study, in keeping with the policies of the hospital.

          6. Reliable telephone access to receive calls from an interactive voice response system
             (IVR) (only applicable to patients who will participate in optional symptom burden
             assessment).

        Exclusion Criteria:

          1. New York Heart Association (NYHA) cardiac class 3-4 heart disease as well as impaired
             cardiac function defined as: left ventricular ejection fraction (LVEF) < 45% as
             determined by Multigated Acquisition Scan (MUGA) scan or electrocardiogram; Complete
             left bundle branch block; Use of cardiac pacemaker; ST depression of > 1 mm in 2 or
             more leads and/or T wave inversions in 2 or more continuous leads; Congenital long QT
             syndrome; History of, or presence of significant ventricular or atrial
             tachyarrhythmia's; Clinically significant resting bradycardia (< 50 bpm); QTc > 450
             msec on screening ECG (using the QTcF formula);

          2. (Continued from #1) Right bundle branch block plus left anterior hemiblock, bivascular
             block; Myocardial infarction within 12 months prior to starting AMN107; Unstable
             angina diagnosed or treated within the past 12 months; Other clinically significant
             heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of
             labile hypertension, or history of poor compliance with an antihypertensive regimen).

          3. Patients with active, uncontrolled psychiatric disorders including: psychosis, major
             depression, and bipolar disorders.

          4. Female patients of childbearing potential must have negative pregnancy test within 7
             days before initiation of study drug dosing. Postmenopausal women must be amenorrheic
             for at least 12 months to be considered of non-childbearing potential. Surgical
             sterilization is considered non-childbearing potential. Female patients of
             reproductive potential must agree to employ an effective method of birth control
             (hormonal or barrier) throughout the study and for up to 3 months following
             discontinuation of study drug.

          5. Patients with severe and/or uncontrolled medial disease (i.e., uncontrolled diabetes,
             chronic renal disease, or active uncontrolled infection [persistent fever and
             worsening clinical condition]).

          6. Patient with known chronic liver disease (i.e., chronic active hepatitis, and
             cirrhosis).

          7. Patient with known diagnosis of human immunodeficiency virus (HIV) infection.

          8. Patients in late chronic phase (i.e., time from diagnosis to treatment >12 months) or
             blastic phase are excluded. The definitions of CML phases are as follows: A. Early
             chronic phase: time from diagnosis to therapy < 12 months Late chronic phase: time
             from diagnosis to therapy > 12 months.B. Blastic phase: presence of 30% blasts or more
             in the peripheral blood or bone marrow. C. Accelerated phase CML: presence of any of
             the following features: * Peripheral or marrow blasts 15% or more.

          9. (Cont. #8)Peripheral or marrow basophils 20% or more. *Thrombocytopenia < 100 x
             10(9)/L unrelated to therapy. * Documented extramedullary blastic disease outside
             liver or spleen due to past causes D. Clonal evolution defined as the presence of
             additional chromosomal abnormalities other than the Ph chromosome is part of
             accelerated phase CML. Ph chromosome variants or complex Ph chromosome translocations
             are not considered to indicate disease acceleration.

         10. ( Cont # 8) We have recently found clonal evolution to have a variable prognostic
             impact and may be suppressed with Interferon therapy (IFN-a therapy). Hence these
             patients, like others with de novo accelerated phase, will be eligible, and analyzed
             separately.