Clinical Trial: Tipifarnib and Bortezomib in Treating Patients With Acute Leukemia or Chronic Myelogenous Leukemia in Blast Phase

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase I Dose-Escalation Study of R115777 (Tipifarnib) Plus PS-341 (Bortezomib) in Relapsed or Refractory Acute Leukemias

Brief Summary: 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.

Detailed Summary:

PRIMARY OBJECTIVE:

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.

SECONDARY OBJECTIVES:

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.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Dose-limiting toxicity and maximum tolerated dose of tipifarnib and bortezomib [ Time Frame: 21 days ]

Original Primary Outcome:

Current Secondary Outcome:

  • Changes in apoptotic protein expression (Bim, Bax, AKT) [ Time Frame: Baseline and day 8 ]
  • Clinical efficacy (response rate) evaluated using the revised International Working Group Criteria (IWG) for AML [ Time Frame: Up to 3 years ]
  • Farnesytransferase and proteasome inhibition in peripheral blood mononuclear cells [ Time Frame: Day 8 ]
  • Farnesytransferase and proteasome inhibition in peripheral blood mononuclear cells [ Time Frame: Day 15 ]


Original Secondary Outcome:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: September 29, 2006
Date Started: August 2006
Date Completion:
Last Updated: April 14, 2015
Last Verified: April 2013