Effect of Imatinib Mesylate and the Pharmacokinetics of Acetaminophen/Paracetamol in Patients With Newly Diagnosed, Previously Untreated Chronic Myeloid Leukemia in Chronic Phase (CML-CP)

A Non-randomized, Open-label Study to Investigate the Effects of Imatinib Mesylate on the Pharmacokinetics of Acetaminophen/Paracetamol in Patients With Newly Diagnosed, Previously Untreated Chronic Myeloid Leukemia in Chronic Phase (CML-CP)

A non-randomized, open-label study to investigate the effects of imatinib mesylate on the pharmacokinetics of acetaminophen/paracetamol in patients with newly diagnosed, previously untreated chronic myeloid leukemia in chronic phase (CML-CP)

Inclusion criteria:

• Ability to provide written informed consent prior to participation to the study.
• Male or female patients ≥ 18 and ≤ 75 years of age
• Patients with CML-CP within 6 months of diagnosis (date of initial diagnosis is the date of first cytogenetic analysis). FISH analysis will not be accepted.
• Diagnosis of CML in chronic phase with cytogenetic confirmation of Philadelphia chromosome of (9;22) translocations and presence of Bcr-Abl
• Documented chronic phase CML as defined by:
• < 15% blasts in peripheral blood and bone marrow
• < 30% blasts plus promyelocytes in peripheral blood and bone marrow
• < 20% basophils in the peripheral blood
• ≥ 100 x 109/L (≥ 100,000 /mm3) platelets
• No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly
• Adequate end organ function as defined by:
• total bilirubin < 1.5 x ULN
• SGOT and SGPT < 2.5 x UNL
• creatinine < 1.5 x ULN
• Female patients of childbearing potential must have a negative serum pregnancy test within 7 days before initiation of study drug

Exclusion criteria:

• Patients in late chronic phase, accelerated phase, or blastic phase are excluded
• Patients who have received other investigational agents
• Patients who received imatinib for any duration prior to study entry
• Patient received any treatment for CML prior to study entry for longer than 2 weeks with the exception of hydroxyurea and/or anagrelide
• Patients with another primary malignancy except if the other primary malignancy is neither currently clinically significant or requiring active intervention
• Patients who are:
• pregnant
• breast feeding
• of childbearing potential without a negative pregnancy test prior to baseline
• male or female of childbearing potential unwilling to use barrier contraceptive precautions throughout the trial
• Post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential
• Patient with a severe or uncontrolled medical condition (i.e., uncontrolled diabetes, chronic renal disease)
• Patient previously received radiotherapy to ≥ 25% of the bone marrow
• Patient had major surgery within 4 weeks prior to study entry, or who have not recovered from prior major surgery
• Patients with an ECOG Performance Status Score ≥ 3
• Patients with International normalized ratio (INR) or partial thromboplastin time (PTT) > 1.5 x IULN, with the exception of patients on treatment with oral anticoagulant
• Patients with known positivity for human immunodeficiency virus (HIV)
• baseline testing for HIV is not required
• Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent
• Patients with identified sibling donors where allogeneic bone marrow transplant is elected as first line treatment
• Patients who are chronic users of acetaminophen or medications containing acetaminophen.
• Patients who received acetaminophen or medications containing acetaminophen within 72 hours prior to study entry.

Other protocol-defined inclusion/exclusion criteria may apply