Chronic Myelomonocytic LeukemiaPhase 1NCT00005845
Tipifarnib in Treating Patients With Myelodysplastic Syndromes
A Phase 1 study testing tipifarnib, laboratory biomarker analysis and pharmacological study in people with Chronic Myelomonocytic Leukemia and de Novo Myelodysplastic Syndromes, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This phase I trial studies the side effects and best dose of tipifarnib in treating patients with myelodysplastic syndromes. Tipifarnib 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
- Chronic Myelomonocytic Leukemia, de Novo Myelodysplastic Syndromes, Previously Treated Myelodysplastic Syndromes
- What is being tested?
- tipifarnib, laboratory biomarker analysis and pharmacological study
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 65 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2002to Sep 2009
- 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
- Patients must have histologically MDS (including French-American-British [FAB] types refractory anemia [RA], refractory anemia with ringed sideroblasts [RARS], refractory anemia with excess blasts [RAEB], refractory anemia with excess blasts in transformation [RAEBT], or chronic myelomonocytic leukemia [CMMoL]); for the purpose of the study, all patients will be classified by World Health Organization (WHO) criteria
- By these criteria, FAB RA are split into:
- Pure dyserythropoietic refractory anemia (PRA)
- Refractory cytopenia with multilineage dysplasia (RCMD)
- FAB RARS is split into:
- Pure sideroblastic anemia (PSA)
Show all 19Show fewer
- Refractory sideroblastic cytopenia with multilineage dysplasia (RSCMD)
- FAB RAEB is split into:
- RAEB I (< 10% BM blasts)
- RAEB II (10-20% BM blasts)
- Patients with CMMoL, and RAEBT by FAB classification will be included in the protocol
- Prognosis will be assessed by International Prognostic Scoring System (IPSS) criteria
- =< 2 prior therapies
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Life expectancy of greater than 12 weeks
- Bilirubin =< 1.5mg %
- Creatinine =< 1.5mg %
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- Patients who have had chemotherapy or radiotherapy within 4 weeks (3 months for UCN01) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients may not be receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to R115777 (such as imidazoles)
- Patients eligible for bone marrow transplant (=< 60 years old), with a compatible sibling, no contraindications for transplant
- Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with R115777.
- Growth factors other than filgrastim (G-CSF) are excluded; patients should be off excluded growth factors for 2 weeks
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I Study of the Farnesyl Transferase Inhibitor R115777 (NSC #702818) in Patients With Myelodysplastic Syndrome
This phase I trial studies the side effects and best dose of tipifarnib in treating patients with myelodysplastic syndromes. Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the toxicity profile and antitumor activity of the farnesyltransferase (FTase) inhibitor R115777 (tipifarnib) in patients with myelodysplastic syndrome (MDS) treated on a one week on/one week off schedule.
II. To determine the effect on R115777 on a one week on/one week off schedule on FTase activity, prenylation of RAS and other substrates and on downstream effects.
OUTLINE: This is a dose-escalation study.
Patients receive tipifarnib orally (PO) twice daily (BID) on weeks 1, 3, 5, and 7. Treatment repeats every 8 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.
- Conditions
- Chronic Myelomonocytic Leukemia, de Novo Myelodysplastic Syndromes, Previously Treated Myelodysplastic Syndromes, Refractory Anemia, Refractory Anemia With Excess Blasts, Refractory Anemia With Excess Blasts in Transformation
- Being tested
- tipifarnib, laboratory biomarker analysis, pharmacological study
- Medical subject headings
- Leukemia, Myelomonocytic, Chronic, Anemia, Refractory, Anemia, Refractory, with Excess of Blasts
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 PO
laboratory biomarker analysisOther
Correlative studies
Also called pharmacological studies
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (tipifarnib) | Experimental | Patients receive tipifarnib PO BID on weeks 1, 3, 5, and 7. Treatment repeats every 8 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Receives: Drug: tipifarnib; Other: laboratory biomarker analysis; Other: pharmacological study |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD defined as the next lower dose level at which 2 patients experience dose limiting toxicity (DLT) defined as grade 3 or 4 toxicity according to the Cancer Therapy Evaluation Program Common Toxicity Criteria
The final analysis will report all toxicities by grade, dose, cycle, and by cumulative dose.
Measured: Up to 8.5 years
Response rate
Will be reported overall and by dose level.
Measured: Up to 8.5 years
Secondary outcomes (3)
FTase inhibition
Based on the shape of the relationship (e.g. linear vs saturation vs peak), a dose response analysis will be performed to describe/summarize the relationship (correlation analysis or curve-fitting).
Measured: Up to 8.5 years
Accumulation of unfarnesylated lamin B1
Based on the shape of the relationship (e.g. linear vs saturation vs peak), a dose response analysis will be performed to describe/summarize the relationship (correlation analysis or curve-fitting).
Measured: Up to 8.5 years
Accumulation of RAS proteins
Based on the shape of the relationship (e.g. linear vs saturation vs peak), a dose response analysis will be performed to describe/summarize the relationship (correlation analysis or curve-fitting).
Measured: Up to 8.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2003 (estimated)
- Study startJun 2002
- Primary completionSep 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Myelomonocytic 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
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Razelle Kurzrock, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00005845
- Sponsor's protocol ID
- NCI-2009-01158
- Other IDs
- NCI-2009-01158, CDR0000067862, DM01-582, 5625, U01CA062461
- Status last verified
- Dec 2013
- First submitted
- 2 Jun 2000
- Last updated
- 16 Dec 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of the Farnesyl Transferase Inhibitor R115777 (NSC #702818) in Patients With Myelodysplastic Syndrome
- ClinicalTrials.gov ID
- NCT00005845
- Acronym / sponsor ID
- NCI-2009-01158
- Conditions
- Chronic Myelomonocytic Leukemia, de Novo Myelodysplastic Syndromes, Previously Treated Myelodysplastic Syndromes, Refractory Anemia, Refractory Anemia With Excess Blasts, Refractory Anemia With Excess Blasts in Transformation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jun 2002
- Primary completion
- Sep 2009 (actual)
- First posted
- 29 Aug 2003 (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 studies the side effects and best dose of tipifarnib in treating patients with myelodysplastic syndromes. Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVES:
- To determine the toxicity profile and antitumor activity of the farnesyltransferase (FTase) inhibitor R115777 (tipifarnib) in patients with myelodysplastic syndrome (MDS) treated on a one week on/one week off schedule.
II. To determine the effect on R115777 on a one week on/one week off schedule on FTase activity, prenylation of RAS and other substrates and on downstream effects.
OUTLINE: This is a dose-escalation study.
Patients receive tipifarnib orally (PO) twice daily (BID) on weeks 1, 3, 5, and 7. Treatment repeats every 8 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (tipifarnib) | Experimental | Drug: tipifarnib, Other: laboratory biomarker analysis, Other: pharmacological studyPatients receive tipifarnib PO BID on weeks 1, 3, 5, and 7. Treatment repeats every 8 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Patients must have histologically MDS (including French-American-British [FAB] types refractory anemia [RA], refractory anemia with ringed sideroblasts [RARS], refractory anemia with excess blasts [RAEB], refractory anemia with excess blasts in transformation [RAEBT], or chronic myelomonocytic leukemia [CMMoL]); for the purpose of the study, all patients will be classified by World Health Organization (WHO) criteria
- Prognosis will be assessed by International Prognostic Scoring System (IPSS) criteria
- =< 2 prior therapies
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Life expectancy of greater than 12 weeks
Key exclusion criteria (7 listed)
- Patients who have had chemotherapy or radiotherapy within 4 weeks (3 months for UCN01) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients may not be receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to R115777 (such as imidazoles)
- Patients eligible for bone marrow transplant (=< 60 years old), with a compatible sibling, no contraindications for transplant
- Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
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 PO | Drug | Treatment (tipifarnib) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (tipifarnib) |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Treatment (tipifarnib) |
Primary outcome
MTD defined as the next lower dose level at which 2 patients experience dose limiting toxicity (DLT) defined as grade 3 or 4 toxicity according to the Cancer Therapy Evaluation Program Common Toxicity Criteria
Time frame: Up to 8.5 years
The final analysis will report all toxicities by grade, dose, cycle, and by cumulative dose.
Response rate
Time frame: Up to 8.5 years
Will be reported overall and by dose level.
3 secondary outcomes
FTase inhibition
Time frame: Up to 8.5 years
Accumulation of unfarnesylated lamin B1
Time frame: Up to 8.5 years
Accumulation of RAS proteins
Time frame: Up to 8.5 years
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 16 Dec 2013.
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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.
Razelle Kurzrock principal investigator
M.D. Anderson 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 tipifarnib, laboratory biomarker analysis and pharmacological study in people with Chronic Myelomonocytic Leukemia and de Novo Myelodysplastic Syndromes, 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 19 inclusion and 7 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 16 Dec 2013. 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?
MTD defined as the next lower dose level at which 2 patients experience dose limiting toxicity (DLT) defined as grade 3 or 4 toxicity according to the Cancer Therapy Evaluation Program Common Toxicity Criteria (time frame: Up to 8.5 years). The study lists 2 primary outcomes in all. 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 16 Dec 2013.