Front-line Treatment of Philadelphia Positive (Ph Pos), BCRABL Positive, Chronic Myeloid Leukemia (CML) With Two Tyrosine Kinase Inhibitors (TKI) (Nilotinib and Imotinib) A Phase II Exploratory Multicentric Centre.
- To assess the complete cytogenetic response rate at 12 months in patients with
Philadelphia chromosome- and BCR-ABL-positive early chronic phase chronic myelogenous
leukemia treated with nilotinib and imatinib mesylate.
- To assess the complete cytogenetic response rate at 6 and 24 months in these patients.
- To assess the major and complete molecular response rate at 6, 12, and 24 months in
- To assess the frequency and the types of BCR-ABL kinase domain mutations at 24 months
during and for 3 years after study treatment.
- To assess the rate of failures and the time to failure at 12, 24, and 60 months in
- To assess compliance, toxicity, and adverse events in these patients.
- To understand the relationship between response, gene expression profile, biomarkers,
and drug plasma concentrations in these patients.
OUTLINE: This is a multicenter study.
Patients receive oral nilotinib twice daily in months 1-3, 7-9, 13-15, and 19-21 and oral
imatinib mesylate once daily in months 4-6, 10-12, 16-18, and 22-24. Treatment continues for
24 months in the absence of disease progression or unacceptable toxicity. Patients may be
eligible to continue oral nilotinib and oral imatinib mesylate for up to another 36 months
if it is in the interest of the patient.
Blood samples and bone marrow biopsies are collected periodically for cytogenetic response
by chromosome banding analysis and FISH analysis; real-time quantitative PCR mutational
analysis and single nucleotide polymorphism analysis of BCR-ABL transcripts; and gene
expression profiling and correlative biomarker studies.
After completion of study therapy, patients are followed every 6 months for 3 years and then
every 12 months for 5 years.
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Complete cytogenetic response rate
At 12 months from study entry
Michele Baccarani, MD
Gruppo Italiano Malattie EMatologiche dell'Adulto
Italy: Ethics Committee