Chronic myeloid leukemia (CML) in chronic phase (CP) MedDRA version: 21.1 Level: LLT Classification code 10009015 Term: Chronic myeloid leukemia System Organ Class: 100000004864
Conditions
Sponsors
Fondazione GIMEMA Franco Mandelli ONLUS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Patients with a confirmed diagnosis of BCR/ABL+ CML in chronic phase o Documented chronic phase CML must meet all the following criteria: ? =65 years) yes F.1.3.1 Number of subjects for this age range 200
Exclusion criteria
Exclusion criteria: •Previous treatment with BCR-ABL inhibitors for more than 30 days. •Expression of any atypical BCR-ABL transcripts, instead of the classical P210-encoding type with the e13a2 or the e14a2 junction at screening. •Previous anticancer agents (hydroxyurea, anagrelide, interferon) for CML for more than three months. •Poorly controlled diabetes mellitus (defined as HbA1c >8%) •Prior documented history of coronary heart disease, including myocardial infarction, coronary bypass, coronary stent, and symptomatic angina as defined at page 30 in Exclusion Criteria. •Uncontrolled hypertension •History of peripheral arterial occlusive disease. •History of acute pancreatitis within 12 months of study entry, or a past medical history of chronic pancreatitis. •Patients actively receiving therapy with strong CYP3A4 inhibitors and/or inducers which cannot be either discontinued or switched to a different medication prior to starting study drug. •Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and for which cannot be either safely discontinued or switched to a different medication prior to starting study drug. •Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment. •Patients unable to understand and to comply with study instructions and requirements. •Refusal to give informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The study will investigate in newly diagnosed CP-CML patients the efficacy of NIL frontline therapy vs IM followed by switch to NIL in the case of absence of optimal response as defined by the ELN criteria using two primary end-points: - To evaluate the rates of molecular response (MR4.5) at 24 months - To evaluate the rate of patients who remain in sustained treatment free remission (=MR3.0) without molecular relapse 12 months after entering the TFR phase. The molecular relapse is defined as loss of MMR, or confirmed loss of MR3.0 ;Secondary Objective: Monitoring the molecular response. Progression-free survival (PFS) in the two arms of the study. Overall Survival in the two arms of the study. Rates of major molecular response (MR3.0) during the study in the two arms of the study. The dynamics of molecular response The relationship between baseline characteristics and the primary objectives The relationship between early molecular response and the primary objectives To assess the safety profile of both arms. To determine the rate and the time-distribution of the discontinuation causes of the first-line TKI. To investigate quality of life (QoL) differences between treatment arms over time ;Primary end point(s): - To evaluate the rates of molecular response (MR4.5) at 24 months - To evaluate the rate of patients who remain in sustained treatment free remission (=MR3.0) without molecular relapse 12 months after entering the TFR phase. ;Timepoint(s) of evaluation of this end point: At 24 months for the rates of molecular response (MR4.5) and at 12 months after entering the TFR phase for the rate of patients who remain in sustained treatment free remission (=MR3.0) without molecular relapse. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - To determine the depth of molecular response by 4 years. - To estimate progression-free survival (PFS) in the two arms of the study at 60 months. - To estimate the Overall Survival in the two arms of the study at 60 months. - To determine the rates of major molecular response (MR3.0) at 1, 2, 3, and 4 year in the two arms of the study. - The dynamics of molecular response - The relationship between baseline characteristics and the achievement of MR4.5 (after treatment NIL frontline therapy vs IM followed by switch to NIL) and the sustained treatment free remission rate (=MR3.0); - The relationship between early molecular response and the achievement of MR4.5 (after treatment NIL frontline therapy vs IM followed by switch to NIL) and the sustained treatment free remission rate (=MR3.0) - To assess the safety profile of either NIL and IM arms. - To determine the rate and the time-distribution of the discontinuation of the first-line TKI, for side-effects, toxicity and AEs. - To investigate quality of life (QoL) differences between treatment arms over time. ;Timepoint(s) of evaluation of this end point: During the study | — |
Countries
Belgium, Italy, Netherlands
Contacts
Public ContactGIMEMA Data Center
GIMEMA Data Center
Outcome results
None listed