Essential ThrombocythemiaPhase 2NCT00047190
Tipifarnib in Treating Patients With Myelofibrosis and Myeloid Metaplasia
A Phase 2 study testing tipifarnib and laboratory biomarker analysis in people with Essential Thrombocythemia and Polycythemia Vera, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Phase II trial to study the effectiveness of tipifarnib in treating patients who have myelofibrosis with myeloid metaplasia. Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Essential Thrombocythemia, Polycythemia Vera, Primary Myelofibrosis
- 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
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2002to Apr 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
- Histopathologic confirmation (on bone marrow trephine and aspirate) of myelofibrosis with myeloid metaplasia by a pathologist/hematologist at the registering institution; included in the diagnosis of MMM are AMM (agnogenic myeloid metaplasia), PPMM (post-polycythemic myeloid metaplasia), and PTMM (post-thrombocythemic myeloid metaplasia); the bone marrow should show the presence of reticulin fibrosis, and the peripheral blood smear should show the presence of leukoerythroblastosis and dacrocytosis
- Bone marrow showing no evidence of other conditions associated with myelofibrosis, such as metastatic carcinoma, lymphoma, myelodysplasia, hairy cell leukemia, mast cell disease, acute leukemia (including M7 type), or acute myelofibrosis
- Bone marrow chromosome analysis or peripheral blood or bone marrow Fluorescent In Situ Hybridization (FISH) showing absence of chromosomal translocation t(9:22); prior demonstration is sufficient for enrollment purposes
- At least one of the following:
- Anemia evidenced by hemoglobin < 10 g/dL
- Palpable hepato-splenomegaly
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- ANC ≥ 750/mm^3
- PLT ≥ 100,000/mm^3
- Total bilirubin (direct if total elevated) ≤ UNL
- Alkaline phosphatase =< 3 x UNL (unless felt to be secondary to disease)
- AST ≤ 2.5 x UNL
- Creatinine =< 1.5 x UNL
- Ability to understand and the willingness to sign a written informed consent document
- Willingness to follow the schedule for returning to the registering P2C institution (monthly) while receiving protocol treatment
- ECOG performance status 0, 1, or 2
Who cannot join
- Any of the following as this regimen may be harmful to a developing fetus or nursing child:
- Pregnant women
- Breastfeeding women
- Men or women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.)
- NOTE: The effects of the agent(s) on the developing human fetus at the recommended therapeutic dose are unknown
- Use of cytotoxic chemotherapy or other myelosuppressive agents within =< 2 weeks prior to study entry
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- Uncontrolled intercurrent illness or any co-morbid condition that would limit compliance with study requirements or with which the use of R115777 is felt to be potentially harmful; such conditions include, but are not limited to:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia, or
- Psychiatric illness/social situations
- Other concurrent therapy directed at the disease (including Thalidomide) or use of erythropoietin while enrolled in this study; such agents must be discontinued at the time of or prior to study entry
- Known quinolone sensitivity
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Trial of R115777 in Myelofibrosis With Myeloid Metaplasia (MMM)
Phase II trial to study the effectiveness of tipifarnib in treating patients who have myelofibrosis with myeloid metaplasia. Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate the response rate in MMM patients treated with R115777. II. To evaluate the toxicity of R115777 in patients with MMM.
SECONDARY OBJECTIVES:
- To evaluate the benefit of therapy with R115777 in alleviating disease-associated anemia in patients with MMM.
II. To evaluate the benefit of R115777 in reducing palpable splenomegaly in patients with MMM.
III. To evaluate the effect of R115777 on the hypercatabolic symptoms from MMM. IV. To evaluate the effect of R115777 on the pathologic increase in circulating myeloid progenitors in MMM patients through baseline measurement and measurement after the first cycle.
- To correlate response/relapse with in vitro myeloid colony sensitivity to R115777 at the time of either response or relapse.
VI. To evaluate the effect of R115777 on bone marrow histologic features of MMM including osteosclerosis, reticulin fibrosis, and angiogenesis (through serial bone marrow microvessel density grading).
OUTLINE: This is a multicenter study.
Patients receive oral tipifarnib twice daily on days 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months until disease progression and then every 6 months for up to 2 years.
PROJECTED ACCRUAL: A total of 18-35 patients will be accrued for this study within 15 months.
- Being tested
- tipifarnib, laboratory biomarker analysis
- Medical subject headings
- Thrombocythemia, Essential, Polycythemia Vera, Primary Myelofibrosis
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
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | Patients receive oral tipifarnib twice daily on days 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Receives: Drug: tipifarnib; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Confirmed response defined as the objective status of complete response (CR) or partial response (PR) on 2 consecutive evaluations at least 4 weeks apart
Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.
Measured: Up to 2 years
Secondary outcomes (3)
Overall survival
Estimated using the method of Kaplan-Meier.
Measured: Time from registration to death due to any cause, assessed up to 2 years
Time to progression
Estimated using the method of Kaplan-Meier.
Measured: Time from registration to the time of progression, assessed up to 2 years
Duration of response
Measured: Date of complete response to the date progression is documented (if one has occurred) or to the date of last follow-up (for those patients who have not progressed), assessed up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startAug 2002
- Primary completionApr 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Essential ThrombocythemiaStudies 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
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Ruben Mesa, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00047190
- Sponsor's protocol ID
- NCI-2012-02804
- Other IDs
- MC0184, N01CM17104
- Status last verified
- Jun 2013
- First submitted
- 3 Oct 2002
- Last updated
- 4 Jun 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of R115777 in Myelofibrosis With Myeloid Metaplasia (MMM)
- ClinicalTrials.gov ID
- NCT00047190
- Acronym / sponsor ID
- NCI-2012-02804
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Aug 2002
- Primary completion
- Apr 2007 (actual)
- First posted
- 27 Jan 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.
Phase II trial to study the effectiveness of tipifarnib in treating patients who have myelofibrosis with myeloid metaplasia. Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth.
Detailed description
PRIMARY OBJECTIVES:
- To evaluate the response rate in MMM patients treated with R115777. II. To evaluate the toxicity of R115777 in patients with MMM.
SECONDARY OBJECTIVES:
- To evaluate the benefit of therapy with R115777 in alleviating disease-associated anemia in patients with MMM.
II. To evaluate the benefit of R115777 in reducing palpable splenomegaly in patients with MMM.
III. To evaluate the effect of R115777 on the hypercatabolic symptoms from MMM. IV. To evaluate the effect of R115777 on the pathologic increase in circulating myeloid progenitors in MMM patients through baseline measurement and measurement after the first cycle.
- To correlate response/relapse with in vitro myeloid colony sensitivity to R115777 at the time of either response or relapse.
VI. To evaluate the effect of R115777 on bone marrow histologic features of MMM including osteosclerosis, reticulin fibrosis, and angiogenesis (through serial bone marrow microvessel density grading).
OUTLINE: This is a multicenter study.
Patients receive oral tipifarnib twice daily on days 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months until disease progression and then every 6 months for up to 2 years.
PROJECTED ACCRUAL: A total of 18-35 patients will be accrued for this study within 15 months.
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 receive oral tipifarnib twice daily on days 1-21. Treatment repeats every 28 days for up to 6 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 (15 listed)
- Histopathologic confirmation (on bone marrow trephine and aspirate) of myelofibrosis with myeloid metaplasia by a pathologist/hematologist at the registering institution; included in the diagnosis of MMM are AMM (agnogenic myeloid metaplasia), PPMM (post-polycythemic myeloid metaplasia), and PTMM (post-thrombocythemic myeloid metaplasia); the bone marrow should show the presence of reticulin fibrosis, and the peripheral blood smear should show the presence of leukoerythroblastosis and dacrocytosis
- Bone marrow showing no evidence of other conditions associated with myelofibrosis, such as metastatic carcinoma, lymphoma, myelodysplasia, hairy cell leukemia, mast cell disease, acute leukemia (including M7 type), or acute myelofibrosis
- Bone marrow chromosome analysis or peripheral blood or bone marrow Fluorescent In Situ Hybridization (FISH) showing absence of chromosomal translocation t(9:22); prior demonstration is sufficient for enrollment purposes
- At least one of the following:
- ANC ≥ 750/mm^3
Key exclusion criteria (14 listed)
- Any of the following as this regimen may be harmful to a developing fetus or nursing child:
- Use of cytotoxic chemotherapy or other myelosuppressive agents within =< 2 weeks prior to study entry
- Uncontrolled intercurrent illness or any co-morbid condition that would limit compliance with study requirements or with which the use of R115777 is felt to be potentially harmful; such conditions include, but are not limited to:
- Other concurrent therapy directed at the disease (including Thalidomide) or use of erythropoietin while enrolled in this study; such agents must be discontinued at the time of or prior to study entry
- Known quinolone sensitivity
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 | Arm I |
| laboratory biomarker analysisCorrelative studies | Other | Arm I |
Primary outcome
Confirmed response defined as the objective status of complete response (CR) or partial response (PR) on 2 consecutive evaluations at least 4 weeks apart
Time frame: Up to 2 years
Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.
3 secondary outcomes
Overall survival
Time frame: Time from registration to death due to any cause, assessed up to 2 years
Time to progression
Time frame: Time from registration to the time of progression, assessed up to 2 years
Duration of response
Time frame: Date of complete response to the date progression is documented (if one has occurred) or to the date of last follow-up (for those patients who have not progressed), assessed up to 2 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 4 Jun 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.
Ruben Mesa principal investigator
Mayo Clinic
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 Essential Thrombocythemia and Polycythemia Vera, 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 15 inclusion and 14 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 4 Jun 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 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 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?
Confirmed response defined as the objective status of complete response (CR) or partial response (PR) on 2 consecutive evaluations at least 4 weeks apart (time frame: Up to 2 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 4 Jun 2013.