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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00383474
First received: September 29, 2006
Last updated: April 9, 2013
Last verified: April 2013

September 29, 2006
April 9, 2013
August 2006
June 2012   (final data collection date for primary outcome measure)
Dose-limiting toxicity and maximum tolerated dose of tipifarnib and bortezomib [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
Not Provided
Complete list of historical versions of study NCT00383474 on ClinicalTrials.gov Archive Site
  • 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 ]
Not Provided
Not Provided
Not Provided
 
Tipifarnib and Bortezomib in Treating Patients With Acute Leukemia or Chronic Myelogenous Leukemia in Blast Phase
A Phase I Dose-Escalation Study of R115777 (Tipifarnib) Plus PS-341 (Bortezomib) in Relapsed or Refractory Acute Leukemias

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.

Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
  • Drug: tipifarnib
    Given orally
    Other Names:
    • R115777
    • Zarnestra
  • Drug: bortezomib
    Given IV
    Other Names:
    • LDP 341
    • MLN341
    • VELCADE
  • Other: laboratory biomarker analysis
    Correlative studies
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.
Interventions:
  • Drug: tipifarnib
  • Drug: bortezomib
  • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
35
Not Provided
June 2012   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00383474
NCI-2009-00147, MCC-14796, CDR0000502258, N02CO12400, N01CM62208
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Jeffrey Lancet H. Lee Moffitt Cancer Center and Research Institute
National Cancer Institute (NCI)
April 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP