Safety and Efficacy of Imatinib in Combination With High Dose Chemotherapy for Acute Phase Chronic Myelogenous Patients

Phase I/II Trial to Study the Dose, Tolerability and the Effectiveness of Imatinib in Combination With Daunorubicine and Cytarabine for Patients With Chronic Myelogenous Leukemia in Myeloid Acute Phase

The aim of this phase I/II trial is to determine the dose of daunorubicine to be associated with cytarabine and Imatinib for induction therapy in patients with chronic myelogenous leukemia in myeloid acute phase.

Study design Imatinib: starting at day -3: 600mg/day; continuous administration In combination with cytarabine: continuous iv/24h: 100mg/m² ; 7 days and daunorubicine: 4 levels

level 1: 0

level 2: 15mg/m² ; 3 days

level 3: 30mg/m² ; 3 days

level 4: 45mg/m² ; 3 days

Inclusion Criteria:

• CML Ph+ (assessed by cytogenetic or FISH)
• Acute phase with ≥ 20% bone marrow blasts (M0 to M6 , excluding M3)
• Age ≥ 18 year at inclusion
• PS grade 0 to 2 (ECOG)
• Adequate and organ function, defined as the following: total bilirubin <1.5x uln, sgpt <3x uln, creatinine <1.5x uln.
• Informed consent signed up

Exclusion Criteria:

• active malignancy other than CML or non-melanoma cancer of the skin
• current treatment with another investigational agent
• 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 performans status 3-4