Adult Acute Basophilic LeukemiaPhase 1NCT00383474
Tipifarnib and Bortezomib in Treating Patients With Acute Leukemia or Chronic Myelogenous Leukemia in Blast Phase
A Phase 1 study testing Bortezomib, Laboratory Biomarker Analysis and Tipifarnib in people with Adult Acute Basophilic Leukemia and Adult Acute Eosinophilic Leukemia, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Acute Basophilic Leukemia, Adult Acute Eosinophilic Leukemia, Adult Acute Megakaryoblastic Leukemia
- What is being tested?
- Bortezomib, Laboratory Biomarker Analysis and Tipifarnib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2006to Jun 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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
- Being tested
- Bortezomib, Laboratory Biomarker Analysis, Tipifarnib
- Medical subject headings
- Leukemia, Basophilic, Acute, Leukemia, Eosinophilic, Acute, Leukemia, Megakaryoblastic, Acute, Leukemia, Monocytic, Acute, Leukemia, Myelomonocytic, Acute, Leukemia, Myeloid, Acute, Leukemia, Erythroblastic, Acute, Blast Crisis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BortezomibDrug
Also called [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
TipifarnibDrug
Also called R115777, Zarnestra
Given orally
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | 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. Receives: Drug: Bortezomib; Other: Laboratory Biomarker Analysis; Drug: Tipifarnib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting toxicity and maximum tolerated dose of tipifarnib and bortezomib
Measured: 21 days
Secondary outcomes (4)
Changes in apoptotic protein expression (Bim, Bax, AKT)
Measured: Baseline and day 8
Clinical efficacy (response rate) evaluated using the revised International Working Group Criteria (IWG) for AML
Measured: Up to 3 years
Farnesytransferase and proteasome inhibition in peripheral blood mononuclear cells
Measured: Day 8
Farnesytransferase and proteasome inhibition in peripheral blood mononuclear cells
Measured: Day 15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2006 (estimated)
- Study startAug 2006
- Primary completionJun 2012
- Study completionJun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adult Acute Basophilic LeukemiaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Jeffrey Lancet, Principal investigator, Moffitt Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00383474
- Sponsor's protocol ID
- NCI-2009-00147
- Other IDs
- NCI-2009-00147, CDR0000502258, MCC-14796, 7306, N01CM62208, P30CA076292
- Status last verified
- Apr 2013
- First submitted
- 29 Sep 2006
- Last updated
- 15 Apr 2015
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Dose-Escalation Study of R115777 (Tipifarnib) Plus PS-341 (Bortezomib) in Relapsed or Refractory Acute Leukemias
- ClinicalTrials.gov ID
- NCT00383474
- Acronym / sponsor ID
- NCI-2009-00147
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Aug 2006
- Primary completion
- Jun 2012 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 3 Oct 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Drug: Bortezomib, Other: Laboratory Biomarker Analysis, Drug: TipifarnibPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (33 listed)
- Meets 1 of the following disease-specific criteria:
- 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)
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BortezomibAlso: [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341Given IV | Drug | Arm I |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Arm I |
| TipifarnibAlso: R115777, ZarnestraGiven orally | Drug | Arm I |
Primary outcome
Dose-limiting toxicity and maximum tolerated dose of tipifarnib and bortezomib
Time frame: 21 days
4 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeffrey Lancet principal investigator
Moffitt Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Bortezomib, Laboratory Biomarker Analysis and Tipifarnib in people with Adult Acute Basophilic Leukemia and Adult Acute Eosinophilic Leukemia, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 33 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-limiting toxicity and maximum tolerated dose of tipifarnib and bortezomib (time frame: 21 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2015; AzTrials last refreshed its copy on 8 Nov 2026.