Stage III Chronic Lymphocytic LeukemiaPhase 2NCT00360776
Tipifarnib in Treating Patients With Anemia or Neutropenia and Large Granular Lymphocyte Leukemia
A Phase 2 study testing tipifarnib and laboratory biomarker analysis in people with Stage III Chronic Lymphocytic Leukemia and Stage IV Chronic Lymphocytic Leukemia, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This phase II trial is studying how well tipifarnib works in treating patients with anemia or neutropenia and large granular lymphocyte leukemia. Tipifarnib may stop the growth of leukemia by blocking blood flow to the cancer cells and by blocking some of the enzymes needed for cancer cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stage III Chronic Lymphocytic Leukemia, Stage IV Chronic Lymphocytic Leukemia, T-cell Large Granular Lymphocyte Leukemia
- What is being tested?
- tipifarnib and laboratory biomarker analysis
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Jun 2006to 14 May 2007
- Phase
- Phase 2
- 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
- Diagnosis of T-cell-large granular lymphocyte (LGL) leukemia or natural killer (NK)-LGL leukemia associated with ≥ 1 of the following clinical manifestations:
- Severe neutropenia (i.e., < 500/mm³)
- Neutropenia associated with recurrent infections, meeting 1 of the following criteria: one severe infection requiring hospitalization or at least 2 infections requiring antibiotic therapy
- Symptomatic anemia with significant fatigue with a score of greater than 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status Scale; dyspnea on exertion, but able to walk one flight of stairs without stopping (less than grade 1 respiratory symptoms); cardiac symptoms including worsening of angina or new onset of chest pain
- Transfusion-dependent anemia
- Willing to discontinue use of MTX, Cy, or cyclosporine for 1 month prior to study entry
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- T-cell-LGL leukemia must meet all of the following criteria: CD3+ and CD57+ cells > 300/mm³ or CD8+ cells > 650/mm³ by phenotypic studies of peripheral blood, evidence for clonal T-cell receptor gene rearrangement based on positive flow cytometric analysis, T-cell receptor (TCR)-γ chain polymerase chain reaction (PCR), TCR-Vβ PCR, or by Southern blot analysis
- NK-LGL leukemia must have CD56+ or CD16+ NK cells > 750/mm³ by phenotypic studies of peripheral blood
- Life expectancy > 2 years
- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
- Fertile patients must use effective contraception prior to and during study
- Negative pregnancy test
- Normal kidney and liver function, as determined by the following laboratory results: total bilirubin less than or equal to 2.0 mg/dl; AST (SGOT) and ALT (SGPT) less than or equal to 2.5 times the upper limit of normal; and creatinine less than or equal to 2.0 mg/dl
Who cannot join
- Not pregnant or nursing
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to tipifarnib
- No allergies to imidazoles (e.g., clotrimazole, ketoconazole, miconazole, econazole, fenticonazole, isoconazole, sulconazole, tioconazole, or terconazole)
- No uncontrolled concurrent illness including, but not limited to, any of the following: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric illness or social situations that would limit study compliance
- No other serious medical illness that would limit survival to < 2 years
- No other malignancy within the past 5 years except inactive nonmelanoma skin cancer or carcinoma in situ of the cervix
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- Psychiatric illness that may interfere with study participation
- No other anticancer agents or therapies
- No concurrent antiretroviral therapy for HIV-positive patients
- No other concurrent investigational agents
- No prior tipifarnib or other inhibitors of MAPK signaling intermediates
Trial locations and contacts
1 site in 1 country.
United States1 site
Case Western Reserve University
Cleveland, Ohio, 44106
About this study
Official title: A Phase 2 Study of Tipifarnib in Large Granular Lymphocyte (LGL) Leukemia
This phase II trial is studying how well tipifarnib works in treating patients with anemia or neutropenia and large granular lymphocyte leukemia. Tipifarnib may stop the growth of leukemia by blocking blood flow to the cancer cells and by blocking some of the enzymes needed for cancer cell growth.
Read the detailed description
PRIMARY OBJECTIVES:
- Estimate the complete response rate, partial response rate, and overall response rate in patients with natural killer (NK)- or T-cell-large granular lymphocyte (LGL) leukemia who present with neutropenia or anemia treated with tipifarnib.
SECONDARY OBJECTIVES:
- Determine the toxicity of tipifarnib in these patients. II. Determine the mechanism of treatment responses in these patients through correlative laboratory studies.
OUTLINE: Patients are stratified by disease type (natural killer-large granular lymphocyte [LGL] leukemia vs T-cell-LGL leukemia).
Patients receive oral tipifarnib twice daily on days 1-21. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients are evaluated after completion of course 4. Patients achieving complete response receive 1 additional course of treatment. Patients achieving partial response receive 4 additional courses of treatment in the absence of disease progression or unacceptable toxicity.
Patients undergo blood collection periodically during study for response mechanism studies and other biomarker correlative studies, including mutations of K-ras and N-ras genes.
After completion of study treatment, patients are followed every 6 months for 5 years.
- Conditions
- Stage III Chronic Lymphocytic Leukemia, Stage IV Chronic Lymphocytic Leukemia, T-cell Large Granular Lymphocyte Leukemia
- Being tested
- tipifarnib, laboratory biomarker analysis
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Large Granular Lymphocytic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tipifarnibDrug
Also called R115777, Zarnestra
Given orally
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | Patients will receive tipifarnib by mouth twice a day for 3 weeks. Treatment may repeat every 4 weeks for up to eight courses.
Patients will undergo blood collection periodically for laboratory studies. After finishing treatment, patients will be evaluated every 6 months for 5 years. Receives: Drug: tipifarnib; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response rates to tipifarib defined as the proportion of patients achieving a complete response (CCR) or partial response (PR)
Measured: Up to 5 years
Secondary outcomes (1)
Changes in Ras/ERK and NK receptor expression
Measured: Baseline to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2006 (estimated)
- Study start2 Jun 2006
- Primary completion14 May 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stage III Chronic Lymphocytic 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Thomas Loughran, Principal investigator, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00360776
- Sponsor's protocol ID
- NCI-2009-00086
- Other IDs
- 5402, CDR0000489291, U01CA062502
- Status last verified
- Apr 2017
- First submitted
- 3 Aug 2006
- Last updated
- 5 Apr 2017
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of Tipifarnib in Large Granular Lymphocyte (LGL) Leukemia
- ClinicalTrials.gov ID
- NCT00360776
- Acronym / sponsor ID
- NCI-2009-00086
- Conditions
- Stage III Chronic Lymphocytic Leukemia, Stage IV Chronic Lymphocytic Leukemia, T-cell Large Granular Lymphocyte Leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 25 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 2 Jun 2006 (actual)
- Primary completion
- 14 May 2007 (actual)
- First posted
- 7 Aug 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 II trial is studying how well tipifarnib works in treating patients with anemia or neutropenia and large granular lymphocyte leukemia. Tipifarnib may stop the growth of leukemia by blocking blood flow to the cancer cells and by blocking some of the enzymes needed for cancer cell growth.
Detailed description
PRIMARY OBJECTIVES:
- Estimate the complete response rate, partial response rate, and overall response rate in patients with natural killer (NK)- or T-cell-large granular lymphocyte (LGL) leukemia who present with neutropenia or anemia treated with tipifarnib.
SECONDARY OBJECTIVES:
- Determine the toxicity of tipifarnib in these patients. II. Determine the mechanism of treatment responses in these patients through correlative laboratory studies.
OUTLINE: Patients are stratified by disease type (natural killer-large granular lymphocyte [LGL] leukemia vs T-cell-LGL leukemia).
Patients receive oral tipifarnib twice daily on days 1-21. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients are evaluated after completion of course 4. Patients achieving complete response receive 1 additional course of treatment. Patients achieving partial response receive 4 additional courses of treatment in the absence of disease progression or unacceptable toxicity.
Patients undergo blood collection periodically during study for response mechanism studies and other biomarker correlative studies, including mutations of K-ras and N-ras genes.
After completion of study treatment, patients are followed every 6 months for 5 years.
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: tipifarnib, Other: laboratory biomarker analysisPatients will receive tipifarnib by mouth twice a day for 3 weeks. Treatment may repeat every 4 weeks for up to eight courses. Patients will undergo blood collection periodically for laboratory studies. After finishing treatment, patients will be evaluated every 6 months for 5 years. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Diagnosis of T-cell-large granular lymphocyte (LGL) leukemia or natural killer (NK)-LGL leukemia associated with ≥ 1 of the following clinical manifestations:
- Willing to discontinue use of MTX, Cy, or cyclosporine for 1 month prior to study entry
- T-cell-LGL leukemia must meet all of the following criteria: CD3+ and CD57+ cells > 300/mm³ or CD8+ cells > 650/mm³ by phenotypic studies of peripheral blood, evidence for clonal T-cell receptor gene rearrangement based on positive flow cytometric analysis, T-cell receptor (TCR)-γ chain polymerase chain reaction (PCR), TCR-Vβ PCR, or by Southern blot analysis
- NK-LGL leukemia must have CD56+ or CD16+ NK cells > 750/mm³ by phenotypic studies of peripheral blood
- Life expectancy > 2 years
Key exclusion criteria (11 listed)
- Not pregnant or nursing
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to tipifarnib
- No allergies to imidazoles (e.g., clotrimazole, ketoconazole, miconazole, econazole, fenticonazole, isoconazole, sulconazole, tioconazole, or terconazole)
- No uncontrolled concurrent illness including, but not limited to, any of the following: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric illness or social situations that would limit study compliance
- No other serious medical illness that would limit survival to < 2 years
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 |
|---|---|---|
| tipifarnibAlso: R115777, ZarnestraGiven orally | Drug | Arm I |
| laboratory biomarker analysisCorrelative studies | Other | Arm I |
Primary outcome
Response rates to tipifarib defined as the proportion of patients achieving a complete response (CCR) or partial response (PR)
Time frame: Up to 5 years
1 secondary outcome
Changes in Ras/ERK and NK receptor expression
Time frame: Baseline to 5 years
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2017.
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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.
Thomas Loughran principal investigator
Case Comprehensive 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 2 study testing tipifarnib and laboratory biomarker analysis in people with Stage III Chronic Lymphocytic Leukemia and Stage IV Chronic Lymphocytic 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 13 inclusion and 11 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: stopped early, as of the sponsor's last update on 5 Apr 2017. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was stopped early. Results are not available in the source record.
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?
Response rates to tipifarib defined as the proportion of patients achieving a complete response (CCR) or partial response (PR) (time frame: Up to 5 years). 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 5 Apr 2017.