A Phase I Dose-Escalation Study of R115777 (Tipifarnib) Plus PS-341 (Bortezomib) in Relapsed or Refractory Acute Leukemias
I. Determine the dose-limiting toxicity and maximum tolerated dose of tipifarnib and
bortezomib in patients with relapsed or refractory acute myeloid leukemia, acute
lymphoblastic leukemia, or chronic myeloid leukemia in blast phase.
I. Determine the effect of this regimen on farnesyltransferase and proteasome inhibition in
peripheral blood mononuclear cells in these patients.
II. Determine the clinical efficacy of this regimen in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11 and oral tipifarnib
twice daily on days 1-14. Treatment repeats every 21 days for 6 courses in the absence of
disease progression or unacceptable toxicity. Patients with partial response or stable
disease may continue therapy beyond 6 courses at the discretion of the investigator.
Cohorts of 3-6 patients receive escalating doses of bortezomib and tipifarnib until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Blood is collected periodically for protein expression studies. Bone marrow aspirates
obtained at baseline are examined by immunohistochemistry for Ki-67 activity.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Dose-limiting toxicity and maximum tolerated dose of tipifarnib and bortezomib
H. Lee Moffitt Cancer Center and Research Institute
United States: Food and Drug Administration
|H. Lee Moffitt Cancer Center and Research Institute||Tampa, Florida 33612|