A Phase I-II, Study of RAD001 in Combination With Imatinib (Glivec®/Gleevec™) in Patients With Chronic Myelogenous Leukemia (CML) in Chronic Phase Who Are Not In Complete Cytogenetic Response to Imatinib-Alone at Study Entry
- Determine the safety, tolerability, and biological activity of everolimus when combined
with imatinib mesylate in patients with chronic phase chronic myelogenous leukemia that
is not in complete cytogenetic remission after prior imatinib mesylate. (Phase I)
- Determine, preliminarily, the clinical efficacy of this regimen, in terms of 3-month
improvement by at least one cytogenetic category and the duration of cytogenetic
improvements, in these patients. (Phase II)
- Determine the 6-month rate of cytogenetic improvements in patients treated with this
- Determine the rate of confirmed cytogenetic improvements in patients treated with this
- Determine the rate and duration of major cytogenetic response in patients treated with
- Determine the rate and kinetics of molecular response in patients treated with this
- Correlate genetic variation in drug metabolism genes, leukemia genes, and drug target
genes with response in patients treated with this regimen.
- Determine the pharmacokinetics of this regimen in these patients.
- Determine whether the mTOR pathway activity, as determined by molecular pathologic
examination before and during treatment with this regimen, is predictive of response in
OUTLINE: This is a phase I, non-randomized, open-label, multicenter, dose-escalation study
of everolimus followed by a phase II study. Patients are stratified according to baseline
cytogenetic status (Philadelphia chromosome-positive cells in bone marrow) (>0% and ≤ 95% vs
- Phase I: Patients receive oral everolimus once daily (or once weekly) and oral imatinib
mesylate once daily beginning on day 1. Treatment continues in the absence of disease
progression or unacceptable toxicity.
Cohorts of 4-6 patients receive escalating doses of everolimus until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6
patients experience dose-limiting toxicity.
- Phase II: Patients receive everolimus and imatinib mesylate as in phase I at the MTD.
Patients are followed every 6 months.
PROJECTED ACCRUAL: A total of 4-98 patients (4-34 for phase I and up to 64 for phase II [34
patients with > 0% and ≤ 95% Philadelphia chromosome (Ph)-positive cells and 30 patients
with > 95% Ph-positive cells]) will be accrued for this study.
Masking: Open Label, Primary Purpose: Treatment
Tolerability and biological activity of everolimus and imatinib mesylate every 6 months after completion of study treatment
Meir Wetzler, MD
Roswell Park Cancer Institute
United States: Federal Government
|Roswell Park Cancer Institute||Buffalo, New York 14263|