Tipifarnib and Bortezomib in Treating Patients With Acute Leukemia or Chronic Myelogenous Leukemia in Blast Phase
Adult Acute Basophilic Leukemia
Adult Acute Eosinophilic Leukemia
Adult Acute Megakaryoblastic Leukemia
Adult Acute Monoblastic Leukemia
Adult Acute Monocytic Leukemia
Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11
Adult Acute Myeloid Leukemia With Maturation
Adult Acute Myeloid Leukemia With Minimal Differentiation
Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1
Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL
Adult Acute Myeloid Leukemia Without Maturation
Adult Acute Myelomonocytic Leukemia
Adult Pure Erythroid Leukemia
Recurrent Adult Acute Lymphoblastic Leukemia
Recurrent Adult Acute Myeloid Leukemia
Untreated Adult Acute Lymphoblastic Leukemia
Untreated Adult Acute Myeloid Leukemia
Other: Laboratory Biomarker Analysis
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Dose-Escalation Study of R115777 (Tipifarnib) Plus PS-341 (Bortezomib) in Relapsed or Refractory Acute Leukemias|
- Dose-limiting toxicity and maximum tolerated dose of tipifarnib and bortezomib [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
- Changes in apoptotic protein expression (Bim, Bax, AKT) [ Time Frame: Baseline and day 8 ] [ Designated as safety issue: No ]
- Clinical efficacy (response rate) evaluated using the revised International Working Group Criteria (IWG) for AML [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
- Farnesytransferase and proteasome inhibition in peripheral blood mononuclear cells [ Time Frame: Day 8 ] [ Designated as safety issue: No ]
- Farnesytransferase and proteasome inhibition in peripheral blood mononuclear cells [ Time Frame: Day 15 ] [ Designated as safety issue: No ]
|Study Start Date:||August 2006|
|Study Completion Date:||June 2012|
|Primary Completion Date:||June 2012 (Final data collection date for primary outcome measure)|
Experimental: Arm I
Patients will receive an infusion of bortezomib twice a week for 2 weeks. They will also receive tipifarnib by mouth twice a day for 2 weeks.
Other Names:Other: Laboratory Biomarker Analysis
Correlative studiesDrug: Tipifarnib
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00383474
|United States, Florida|
|Moffitt Cancer Center|
|Tampa, Florida, United States, 33612|
|Principal Investigator:||Jeffrey Lancet||Moffitt Cancer Center|