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.

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.

Inclusion Criteria:

• Meets 1 of the following disease-specific criteria:

  • Relapsed disease after =< 2 prior chemotherapy regimens (consolidation therapy excluded)
  • Primary-induction failure
  • Previously untreated and deemed unfit for or refusing cytotoxic chemotherapy

• No hyperleukocytosis (leukemic blasts >= 30,000/mm^3)

• No acute promyelocytic leukemia (M3)

• No active CNS leukemia

• SGOT and SGPT =< 2 times upper limit of normal (ULN)

• Bilirubin normal

• Creatinine =< 1.5 times ULN

• No uncontrolled hypertension, congestive heart failure, angina pectoris, or ventricular dysrhythmias

• Not pregnant or nursing

• Negative pregnancy test

• No uncontrolled disseminated intravascular coagulation

• Fertile patients must use effective contraception

  • Hormonal contraception must have been initiated ≥ 1 month prior to study entry

• No active graft-vs-host disease

• No active uncontrolled infection

• No intrinsic impaired organ function

• No known allergy to imidazole drugs

• No neuropathy >= grade 1

• No known hypersensitivity to bortezomib, tipifarnib, boron, or mannitol

• No physical or psychiatric conditions that would preclude study participation, including poorly controlled psychosis

• At least 48 hours since prior hydroxyurea

• No prior tipifarnib, bortezomib, or investigational proteasomal inhibitors

• No concurrent radiotherapy, chemotherapy, or immunotherapy

• No concurrent enzyme-inducing antiepileptic medications (e.g., phenytoin, phenobarbital, or carbamazepine)

• ECOG performance status 0-2

• LVEF >= 40%

• Pathologically confirmed diagnosis of 1 of the following:

  • Acute myeloid leukemia
  • Acute lymphoblastic leukemia
  • Chronic myelogenous leukemia in blast phase