The Protein Tyrosine Kinase Inhibitor Nilotinib as First-line Treatment of Ph+ Chronic Myeloid Leucemia (CML) in Early Chronic Phase: a Phase II Exploratory, Multicenter Study. GIMEMA Protocol CML 0307. EUDRACT 2007-000597-22.
Phase II, Prospective, multicentric, non randomized, open label
The primary objective of the trial is to investigate the cytogenetic and molecular effects
of the protein tyrosine kinase (PTK) inhibitor nilotinib in the treatment of early chronic
phase Ph+ CML.
The secondary objectives are:
To investigate in early CP Ph+ CML patients treated with nilotinib the clinical and the
hematologic effects, the effect on bcr/abl point mutations, the kinetic of the response, the
toxicity, the compliance to treatment and the dose density.
This study is an open-label, multicenter, exploratory, Phase II study of nilotinib
administered orally twice daily for one year. For the patients who will benefit an extension
to 4 years is planned.
Visit Schedule and Assessments:
A visit with blood counts and differential and serum chemistry is due baseline, every 15
days for 3 months, hence every 30 days.
An ECG is due baseline, after 15 and 30 days, hence at 60, 90, 150, 240 and 360 days.
An echocardiogram is due baseline and at end-of-study (360 days) or early withdrawal.
A bone marrow aspirate is due baseline (cytology, cytogenetics and quantitative molecular
biology), after 3 and 6 months (cytology and cytogenetics) and after 12 months (cytology,
cytogenetics, quantitative molecular biology and mutational analysis).
A peripheral blood sample is due baseline, at 30, 60, 90, 180, 270 and 360 days for
quantitative molecular biology.
After the end of the study (i.e. after one year) clinical, cytogenetic and molecular data
are due every 6 months.
Bone marrow and peripheral blood cells will be collected before, during and at the end of
the study, stored at the central lab in Bologna and used for molecular assays that are
listed in details in the protocol, with the exclusion of any test allowing the
identification of patients genotype. The samples are kept for a minimum of 10 years and can
be destroyed upon patient request. A specific consent form to the sample storage will be
submitted to the patients.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Complete cytogenetic response (CCgR ) rate
At 1 year
Azienda Ospedaliera Universitaria -Policlincio S. Orsola-Malpighi
Italy: The Italian Medicines Agency