Therapy of Early Chronic Phase Chronic Myelogenous Leukemia (CML) with Oral Nilotinib
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.
Disease Group: Leukemia
Treatment Agent: AMN 107
Treatment Location: Only at MD Anderson
Estimatated Length of Stay in Houston: N/A
Return Visit: Every 3-4 months for 1 year, then every 6-12 months.
Home Care: All therapy is self-administered.
Primary: To determine the percentage of patients who achieve low levels of PCR ratios of Bcr-Abl/Abl (molecular CR) after 12 months of therapy with nilotinib. Secondary: To determine the proportion of patients with Ph-positive early chronic phase CML achieving a complete cytogenetic response after nilotinib therapy, and the time to achieve the response. To evaluate the durations of PCR negativity, cytogenetic response, hematologic control, and survival. To analyze differences in response rates and in prognosis within different risk groups and patient characteristics. To evaluate symptom burden inpatients with CML receiving nilotinib.
IRB Review and Approval Date: APR 20,2005
Recruitment Status: Closed
Projected Accrual: N/A
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 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) ECOG performance of 0-2.
4) Adequate end organ function, defined as the following: total bilirubin < 1.5 x ULN, 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).
1) NYHA cardiac class 3-4 heart disease as well as impaired cardiac
function defined as: LVEF < 45% as determined by 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, bifascular 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 IFN-a therapy. Hence these patients, like others with de novo accelerated phase, will be eligible, and analyzed separately.