Multicenter, Phase III Study Comparing Imatinib (STI571, Glivec®) Standard Dose (400 Mg/Day) With Imatinib High Dose Induction (800 Mg/Day) Followed by Standard Dose Maintenance (400 Mg/Day) in Pretreated CML Patients in Chronic Phase
Patients with CML not achieving or losing a major cytogenetic response on whatever
palliative treatment for CML, are at high risk to progress to accelerated phase and blast
crisis. A new promising treatment with Imatinib (Glivec®), a tyrosine-kinase inhibitor, has
been introduced recently. High rates of hematologic and cytogenetic responses can be
achieved with Imatinib (Glivec®) at > = 300 mg/day in chronic phase CML patients that are
refractory, resistant or intolerant to interferon-alpha. However, about 10 – 20% of these
high risk patients will lose their response to Imatinib (Glivec®) within 1-2 years.
Therefore, improvement of the treatment is warranted.
Since cytogenetic response rate is correlated to survival and the resistance to Imatinib
(Glivec®) might be caused by mutations in the receptor, a more rapid decrease could lead to
longer survival and/or less resistance development. In the initial 6 months of treatment,
monotherapy with Imatinib (Glivec®) with a dose of 800 mg/day (high dose) should be more
effective in the reduction of a high leukemic tumor burden, thereby allowing the residual
normal progenitor and stem cells to expand. In addition, high dose Imatinib (Glivec®) should
further improve the induction of a molecular response, as determined by quantitative reverse
transcription polymerase chain reaction (RT-PCR), reducing the risk of relapse from
residual malignant BCR-ABL positive cells.
This study will investigate the efficacy and tolerability of a short (6 months) high dose
therapy followed by a standard dose compared to a continuous treatment with a standard dose
of Imatinib (Glivec®).
In addition, the dynamics of the molecular and cytogenetic response will be investigated.
Finally, the study will investigate the effect of this induction-maintenance concept on
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine the efficacy regarding major cytogenetic response within 12 months after randomization
Guenther Gastl, MD
Medical University Innsbruck
Austria: Federal Ministry for Health and Women