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

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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

Official Title
-----------------
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

Conditions
-----------------
Chronic Myeloid Leukemia

Intervention / Treatment
-----------------
* Drug: Imatinib mesylate 600 mg
* Drug: Cytarabine
* Drug: Daunorubicine


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Imatinib mesylate 600 mg|nan|
|Drug: Cytarabine|nan|
|Drug: Daunorubicine|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the tolerability and the effectiveness of imatinib in combination with daunorubicine and cytarabine and to determine the recommended dose of daunorubicine to be associated with cytarabine |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| - To evaluate the survival without progression, the survival without event, the overall survival, the hematologic, cytogenetic and molecular responses at various check points. |  |  | 
| - To evaluate duration of responses and failure to respond |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CML, Acute Phase, Imatinib mesylate, Cytarabine, Daunorubicine