Imatinib Alone (IA) Vs. Imatinib + Ara-C (IMAC): A Randomized Phase III Clinical Trial for the Treatment of Early Phase (EP) Chronic Myeloid Leukemia (CML) Ph+. Preliminary Report of Mexican Cooperative Leukemia Group (GRUMELA).

Imatinib mesylate is the standard treatment for chronic phase CML. Imatinib combinations with interferon alpha or Ara-C has shown synergistic anti-proliferative effects. In an attempt to improve the rate of cytogenetic responses we compare the use of IA vs. IMAC as initial therapy in EP (< 12 months) Ph+ CML patients (pts). The study was conducted in 48 Ph+ CML pts recruited within 12 months from diagnosis with no treatment other than alkylating agents and were randomized to receive IA 400 mg/day (N= 23) or imatinib 400 mg/day plus Ara-C (subcutaneous injection) 10 mg/m²/BSA daily for 10 days monthly (N= 25). Median age for IA group is 44 years (18–75) and 38 years (20–57) for IMAC group. Median time from diagnosis of CML to inclusion was 8 months (1–12). Complete Hematologic Response (CHR) was achieved in 20 pts. (86.9%) for the IA group and in 24 patients (96%) of the IMAC group in a median time of 3 weeks (range: 1–6). With a median follow-up of 9 months (range 3–12 months) Cytogenetic Responses (CgR) in group IA were achieved in 69%: Major Cytogenetic Responses (MCgR) (Bcr/Abl 1–35%) assessed by Bone Marrow Fluorescence in situ Hybridization (FISH) (performed pretreatment and at month 3 and 6) were obtained in 11 pts (47.8%) and minor Cytogenetic Response (mCgR) (Bcr/Abl 36–90%) in 5 pts (21.7%). In the IMAC group Cytogenetic Responses were achieved in 92%: MCgR in 16 (64%) and mCgR in 7(28%). Toxicity grade III neutropenia was present in 2 pts (8.6%) of IA group and in 3 pts (12%) for the IMAC group and grade I –II nausea and edema were the most frequent adverse reactions for both groups in about 30 % of cases. Six pts (26.3%) from the IA group has no response compared with 2 (8%) from the IMAC group. Two patients from the IMAC group and 1 from IA were removed due to Cytogenetic Clonal Evolution and lost of CgR. From these preliminary results we suggest that CHR and Global Cytogenetic Response are higher in the IMAC group, meanwhile there is a lower CgR and high rate of Pts with no cytogenetic response (26.3 vs. 8%) in the IA group. It is too early to conclude definitive differences in the cytogenetic responses at this time, but it appears to be a trend to greater CgR rate for the IMAC group. Data collection and patient accrual are ongoing and results with a 18 months follow up will be presented.

Preliminary Results