Phase II Explorative Study of Intermittent Imatinib (IM) Treatment (INTERIM) in Elderly Patients with Ph+ Chronic Myeloid Leukemia (CML) Who Achieved a Stable Complete Cytogenetic Response (CCgR) with Standard IM Therapy

Standard therapy with Imatinib (i.e. daily administration) significantly prolongs the survival of Ph+ CML patients who obtain a complete cytogenetic response (CCgR). Elderly patients (i.e. > 65 yrs) have similar cytogenetic responses and survival, but they usually show a low compliance. This prospective multicenter trial addresses the issue of intermittent administration of Imatinib (INTERIM) in Ph+ CML patients older than 65 years with stable complete cytogenetic response (CCgR) after at least 2 years of standard therapy with IM. Lower doses of IM could be sufficient to maintain the CCgR, to improve the tolerance and to reduce the costs of therapy. For this purpose, IM will be given at the same dose that was given at the time of enrollment by the following intermittent schedule: 1 week on/1 week off for the 1^st month (weeks 1–4); 2 weeks on/2 weeks off for the 2^nd and 3^rd month (weeks 5–12); 1 month on/1 month off from the 4^th month thereafter (weeks 13 on). The primary objective of the study is to evaluate the proportion of patients who remain in CCgR with INTERIM. The cytogenetic response (CgR) status will be evaluated at baseline (by conventional cytogenetics on bone marrow and FISH on peripheral-blood) and every 3 months during the study (only by FISH on peripheral-blood). If FISH documents a variation of the baseline value of more than 1% in two consecutive examinations, evaluation of marrow cells metaphases will be performed to confirm the loss of CCgR and to check for additional cytogenetic abnormalities (ACA). In case of loss of CCgR INTERIM will be stopped and standard therapy (daily administration) will be resumed. Quantitative molecular assessment of BCR-ABL transcript by RQ-PCR on peripheral blood is due at baseline and every 3 months during the study and mutational analysis of ABL will be performed in case of loss of CCgR. After 12 months, the patients who are in continuous CCgR are advised to continue the intermittent study schedule and to be followed indefinitely. The study started in May 2008 and, at present, 18 patients have been enrolled. Preliminary data on the first six months will be presented.