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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00383474
Recruitment Status : Completed
First Posted : October 3, 2006
Last Update Posted : April 15, 2015
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE September 29, 2006
First Posted Date  ICMJE October 3, 2006
Last Update Posted Date April 15, 2015
Study Start Date  ICMJE August 2006
Actual Primary Completion Date June 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 16, 2013)
Dose-limiting toxicity and maximum tolerated dose of tipifarnib and bortezomib [ Time Frame: 21 days ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 14, 2015)
  • 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 Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Tipifarnib and Bortezomib in Treating Patients With Acute Leukemia or Chronic Myelogenous Leukemia in Blast Phase
Official Title  ICMJE 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 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • Drug: Bortezomib
    Given IV
    Other 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
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Drug: Tipifarnib
    Given orally
    Other Names:
    • R115777
    • Zarnestra
Study Arms  ICMJE 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: Bortezomib
  • Other: Laboratory Biomarker Analysis
  • Drug: Tipifarnib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 6, 2007)
35
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE June 2012
Actual Primary Completion Date June 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00383474
Other Study ID Numbers  ICMJE NCI-2009-00147
NCI-2009-00147 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000502258
MCC-14796 ( Other Identifier: Moffitt Cancer Center )
7306 ( Other Identifier: CTEP )
N01CM62208 ( U.S. NIH Grant/Contract )
P30CA076292 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jeffrey Lancet Moffitt Cancer Center
PRS Account National Cancer Institute (NCI)
Verification Date April 2013

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