International, multicenter, randomised, open-labeled, 2-arm - Phase III Study comparing Imatinib (STI571, Glivec®) Standard Dose (400 mg/day) with Imatinib High Dose Induction (800 mg/day) followed by Imatinib Standard Dose Maintenance (400 mg/day) in pretreated Ph+/BCR-ABL+ CML Patients in Chronic Phase - ISTAHIT

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 240

Inclusion Criteria

1.Patients ³ 18 years of age.
2.BCR-ABL positive CML patients in chronic phase, confirmed by caryotype (Ph+) or RT-PCR.
3.Patients pretreated with any drug that is known to control the disease of CML in chronic phase except Imatinib (Glivec®).
4.Patients without a major cytogenetic response at study entry (>35 % Ph+ metaphases in bone marrow cytogenetic analysis performed < 3 months before study entry).
5.Patients either intolerant to Interferon-a (non-hematologic toxicity grade 3-4 for more than 2 weeks) or having received pretreatment for CML at least 12 months before study entry.
6.WHO Status 0-2.
7.Adequate end organ function, defined as the following: Total bilirubin < 1.5 x ULN, SGOT and SGPT < 2.5 x ULN, creatinine < 1.5 x ULN, ANC > 1.5 x 109/L, platelets > 100 x 109/L.
8.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. Male and female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug.
9.Written voluntary informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Patients eligible for allogeneic bone marrow transplantation.
2.Patients in accelerated phase or blast crisis.
3.Known tuberculosis or other uncontrolled infection.
4.Other primary tumor of a different histological origin than the study indication (unless the relapse-free interval is > 5 years, and with the exception of cervical carcinoma in situ (CIS), basal cell epithelioma or squamous cell carcinoma of the skin).
5.Major surgery within the last 14 days.
6.Known to be HIV positive.
7.Unstable medical disorder (except for indication) that excludes the patient in the opinion of the investigator.
8.Patient has received any other investigational agents within 28 days of first day of study drug dosing.
9.Patients with an WHO Performance Status Score > 3 (see Table Section 8.1).
10.Patient with Grade III/IV cardiac problems as defined by the New York Heart Association Criteria (i.e., congestive heart failure, myocardial infarction within 6 months of study).
11.Female patients who are pregnant or breast-feeding.
12.Refusal by female patients of child bearing age to use a safe contraceptive.
13.Patient with known chronic liver disease (i.e. chronic active hepatitis, and cirrhosis).
14. Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine efficacy regarding major cytogenetic response within 12 months after randomization.;Secondary Objective: 1)To determine major cytogenetic response after 3 months vs. 6-12 months after randomization.<br>2)To determine efficacy of the molecular response within 12 and 24 months after randomization.<br>3)To determine time to molecular progression within 24 months.<br>4)To determine dynamics of the molecular response within 3 and 6 months after randomization. expressed as the slope of decrease of bcr/abl-transcripts<br>5)To determine tolerability;Primary end point(s): Major cytogenetic response (MCR), kinetics of cytogenetic and molecular response, time to progression

Secondary Outcome Measures