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

NCT ID: NCT00383474

Last Updated: 2015-04-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-08-31
• Study Completion Date: 2012-06-30

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 Description

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.

Conditions

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 Erythroleukemia; Adult Pure Erythroid Leukemia; Blastic Phase; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Disease; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Bortezomib

Intervention Type: DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Tipifarnib

Intervention Type: DRUG

Given orally

Interventions

Bortezomib

Given IV

Intervention Type: DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Tipifarnib

Given orally

Intervention Type: DRUG

Other Intervention Names

[(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid; LDP 341; MLN341; PS-341; PS341; Velcade; R115777; Zarnestra

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeffrey Lancet

Role: PRINCIPAL_INVESTIGATOR

Moffitt Cancer Center

Locations

Moffitt Cancer Center

Tampa, Florida, United States

Countries

United States

Other Identifiers

NCI-2009-00147

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000502258

Identifier Type: -

Identifier Source: secondary_id

MCC-14796

Identifier Type: OTHER

Identifier Source: secondary_id

7306

Identifier Type: OTHER

Identifier Source: secondary_id

N01CM62208

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA076292

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00147

Identifier Type: -

Identifier Source: org_study_id