Multicenter, Randomized, Phase III Study Comparing Imatinib (Glivec) Standard Dose (400 mg/d) with Imatinib High Dose Induction (800 mg/d) Followed by Imatinib Maintenance (400 mg/d) in Patients with Pretreated Ph⁺/BCR-ABL⁺ CML in Chronic Phase - Results from the First Planned Interim Analysis (CELSG-CML 11 ISTAHIT Study).

227 patients with pretreated Ph⁺/BCR-ABL⁺ CML were randomized into this 2-arm phase III trial comparing standard dose Imatinib (400 mg/d; arm A) with high dose (HD) Imatinib (800 mg/d for 6 months) for induction followed by Imatinib 400 mg/d for maintenance (400 mg/d; arm B). The interim analysis presented here was performed on all patients after 50% of the patients had been treated for 12 months since randomisation. There were no significant differences between treatment arms regarding sex, age and different pretreatments. Rates of complete hematological responses did not differ significantly between both groups at 3, 6 and 12 months (82% arm A, 90% arm B). However, significantly* more patients achieved a major (MCR) and a complete cytogenetic response (CCR) at 3 months (MCR: 21% arm A, 37% arm B; CCR: 6% arm A, 25% arm B) and 6 months (MCR: 34% arm A, 54% arm B; CCR: 20% arm A, 44% arm B). Moreover, significantly* more patients achieved a major molecular response (MMR) at 6 months in the Imatinib HD arm B compared to arm A (20% vs 7%). At 12 months, following dose reduction of Imatinib to 400 mg/d for maintenance at month 6 in the HD arm B, the rates of MCR (the primary endpoint of the study) were comparable (57% arm A, 59% arm B). Nevertheless, there was still a clear trend to higher rates of CCR (37% arm A, 48% arm B) and MMR (16% arm A, 21% arm B) in the HD arm, but at the time of the interim analysis these values did not reach statistical significance. In contrast to non-hematological toxicities, grade 3/4 hematological toxicities were significantly* more common in the HD arm B [anemia: 2% (A), 12% (B); leukopenia: 23% (A), 41% (B), thrombopenia: 14% (A), 34% (B)]. In conclusion, this is the first randomized phase III trial demonstrating significantly* higher rates of MCR, CCR and MMR in chronic phase CML during therapy with HD Imatinib. *p<0.05