A randomized open-label study of 400 mg versus 800 mg of Gleevec/Glivec (imatinib mesylate) in patients with newly diagnosed, previously untreated chronic myeloid leukemia in chronic phase (CML-CP) using molecular endpoints - N/A

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2005-000657-29-CZ
• Date of registration: 24/03/2006
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A randomized open-label study of 400 mg versus 800 mg of Gleevec/Glivec (imatinib mesylate) in patients with newly diagnosed, previously untreated chronic myeloid leukemia in chronic phase (CML-CP) using molecular endpoints - N/A
• Scientific title: A randomized open-label study of 400 mg versus 800 mg of Gleevec/Glivec (imatinib mesylate) in patients with newly diagnosed, previously untreated chronic myeloid leukemia in chronic phase (CML-CP) using molecular endpoints - N/A
• Date of first enrolment: 10/05/2006
• Target sample size: 420
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-000657-29
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Glivec 400mg

Countries of recruitment

Czech Republic, Italy, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
1. Ability to provide written informed consent prior to participation to the study.
2. Male or female patients = 18 and = 75 years of age
3. Patients within 6 months of diagnosis (date of initial diagnosis is the date of first
cytogenetic analysis)
4. Diagnosis of chronic myelogenous leukemia in chronic phase with cytogenetic
confirmation of Philadelphia chromosome of (9;22) translocations and presence of Bcr-Abl
5. 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
hepatospenomegaly
6. 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
7. Female patients of childbearing potential must have a negative serum pregnancy test within 7 days before initiation of study drug.
Are the trial subjects under 18?
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 in late chronic phase, accelerated phase, or blastic phase are excluded
2. Patients who have received other investigational agents
3. Patients who received Gleevec/Glivec for any duration prior to study entry, with the exception of those patients successfully completing [CSTIA2107] study immediately prior to the participation in this study
4. Patient received any treatment for CML prior to study entry for longer than 1 month with the exception of hydroxyurea and/or anagrelide
5. Patients with another primary malignancy except if the other primary malignancy is
neither currently clinically significant or requiring active intervention
6. Patients who are: (a) pregnant, (b) breast feeding, (c) of childbearing potential without a negative pregnancy test prior to baseline and (d) 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).
7. Patient with a severe or uncontrolled medical condition (i.e., uncontrolled diabetes,
chronic renal disease)
8. Patient previously received radiotherapy to = 25% of the bone marrow
9. Patient had major surgery within 4 weeks prior to study entry, or who have not recovered from prior major surgery
10. Patients with an ECOG Performance Status Score = 3
11. Patients with International normalized ratio (INR) or partial thromboplastin time (PTT) >
1.5 x IULN, with the exception of patients on treatment with oral anticoagulants
12. Patients with known positivity for human immunodeficiency virus (HIV); baseline testing for HIV is not required
13. Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent
14. Patients with identified sibling donors where allogeneic bone marrow transplant is elected as first line treatment


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Newly diagnosed Philadelphia chromosome (bcr-abl) positive (Ph+) chronic myeloid leukemia in chronic phase (CML-CP)

Intervention(s)

Trade Name: Glivec 100mg
Product Name: Glivec
Product Code: STI571
Pharmaceutical Form: Tablet
INN or Proposed INN: Imatinib mesilate
CAS Number: 220127-57-1
Current Sponsor code: STI571
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Trade Name: Glivec 400mg
Product Name: Glivec
Product Code: STI571
Pharmaceutical Form: Tablet
INN or Proposed INN: Imatinib mesilate
CAS Number: 220127-57-1
Current Sponsor code: STI571
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-

Primary Outcome(s)

Primary end point(s): Evaluation of the rate of molecular response (MR) at 12 months as measured by log reduction of Bcr-Abl transcript as detected by RT-PCR

Secondary Objective: (for full list see protocol)
•To determine the rate of hematologic response
•To determine the rate of complete cytogenetic response (CCyR)
•To evaluate the time to (CCyR), molecular response, and complete molecular response
•To compare the percentage of patients with a = 3 log reduction in Bcr-Abl transcripts and with undetectable levels at 12 months and yearly thereafter
•To evaluate progression-free survival (PFS) at 5 years
•To evaluate the safety profile of Gleevec/Glivec when given at 800 mg daily administered as 400 mg bid
•To evaluate the actual dose-intensity delivered amongst the two treatment arms
•To validate molecular response (MR) as a prognostic factor for time-to-progression (TTP)
•To evaluate quality of life (QoL) and healthcare resource utilization
•To determine the pharmacokinetic characteristics following 400 mg versus 800 mg
•To investigate tumor-specific mutations

Main Objective: To establish whether 800 mg Gleevec/Glivec (as 400 mg bid) improves efficacy in newly diagnosed, previously untreated CML-CP patients as compared to 400 mg by the evaluation of the rate of molecular response at 12 months as measured by log reduction of Bcr-Abl transcript as detected by RT-PCR

Secondary ID(s)

CSTI571K2301

N/A

2005-000657-29-ES