Phase II Trial of Decitabine in Patients With Chronic Myelogenous Leukemia Chronic Phase Who Are Refractory to Imatinib Mesylate (Gleevec)

A Phase II, Multicenter Study of Decitabine (5-aza-2'Deoxycytidine) in Chronic Myelogenous Leukemia Chronic Phase Refractory to Imatinib Mesylate (STI 571)

To determine the safety and efficacy of decitabine in patients with Philadelphia chromosome-positive chronic myelogenous leukemia chronic phase that were previously treated with imatinib mesylate (STI 571) and became resistant/refractory or were found to be intolerant to the drug.

Inclusion:

• Histologically confirmed diagnosis of CML chronic phase
• Ph chromosome-positive
• Previous treatment with imatinib mesylate resulting in: i) Hematologic Resistance / Hematologic Refractory: Based on a physician's (documented) decision to discontinue imatinib mesylate treatment due to failure of continued benefit or no benefit to the patient, ii) Imatinib Mesylate Intolerance: any toxicity resulting in a physician's (documented) decision to discontinue imatinib mesylate treatment.
• Patients must have recovered from the side effects of previous CML therapy for chronic phase with the exception of hydroxyurea
• Age >/= 2 years
• Bilirubin </= 3 x the upper limit of normal (ULN), SGOT and SGPT </= 3 x ULN, except </= 5 x ULN in leukemic involvement of the liver, serum creatinine </= 2 x ULN
• WHO performance status 0-3
• A negative serum hCG pregnancy test in patients of childbearing potential
• Able to give signed informed consent directly or through a parent or guardian for minors

Exclusion:

• Leukemic involvement of the central nervous system
• Active malignancy other than CML or non-melanoma cancer of the skin
• Previous treatment for CML with another investigational agent within 28 days of study entry
• At study entry, patients who were treated with: imatinib mesylate within the past 48 hours; interferon-alpha within the past 48 hours; homoharringtonine within the past 14 days; low-dose cytosine arabinoside within 7 days, moderate dose within 14 days, or high dose within 28 days; etoposide, anthracyclines, or mitoxantrone within 21 days; busulfan within the past six weeks
• Patients who had received hematopoietic stem cell transplantation within 6 weeks of Day 1 decitabine therapy
• Patients with Grade 3/4 cardiac disease or any other serious concurrent medical condition.
• Patients who are pregnant or nursing. All patients of childbearing potential must practice effective methods of contraception while on study.
• Patients with mental illness or other condition precluding their ability to give informed consent or to comply with study requirements
• Patients with systemic, uncontrolled infections