Phase II Nilotinib With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia (CML)

• Status: Completed
• Trial end date: 2018-07-11
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborator: Novartis

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.