Tipifarnib and Bortezomib in Treating Patients With Acute Leukemia or Chronic Myelogenous Leukemia in Blast Phase
This phase I trial is studying the side effects and best dose of tipifarnib and bortezomib in treating patients with acute leukemia or chronic myelogenous leukemia in blast phase. Tipifarnib and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving tipifarnib together with bortezomib may kill more cancer cells.
Adult Acute Basophilic Leukemia
Adult Acute Eosinophilic Leukemia
Adult Acute Megakaryoblastic Leukemia (M7)
Adult Acute Minimally Differentiated Myeloid Leukemia (M0)
Adult Acute Monoblastic Leukemia (M5a)
Adult Acute Monocytic Leukemia (M5b)
Adult Acute Myeloblastic Leukemia With Maturation (M2)
Adult Acute Myeloblastic Leukemia Without Maturation (M1)
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
Adult Acute Myelomonocytic Leukemia (M4)
Adult Erythroleukemia (M6a)
Adult Pure Erythroid Leukemia (M6b)
Blastic Phase Chronic Myelogenous Leukemia
Recurrent Adult Acute Lymphoblastic Leukemia
Recurrent Adult Acute Myeloid Leukemia
Relapsing Chronic Myelogenous 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 ]
- 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 ]
- 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 ]
|Study Start Date:||August 2006|
|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:Drug: bortezomib
Other Names:Other: laboratory biomarker analysis
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|
|H. Lee Moffitt Cancer Center and Research Institute|
|Tampa, Florida, United States, 33612|
|Principal Investigator:||Jeffrey Lancet||H. Lee Moffitt Cancer Center and Research Institute|