Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic SyndromePhase 2NCT00027872
Tipifarnib in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia
A Phase 2 study testing tipifarnib and laboratory biomarker analysis in people with Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome and Adult Acute Basophilic Leukemia, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Tipifarnib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Phase II trial to study the effectiveness of tipifarnib in treating older patients who have previously untreated acute myeloid leukemia Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome, Adult Acute Basophilic Leukemia, Adult Acute Eosinophilic 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
- 125 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2001to Jan 2009
- 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 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Pathologic confirmation of the diagnosis of AML (>= 20% marrow blasts)
- ECOG performance status 0 or 1
- Patients must be able to give informed consent
- SGOT and SGPT =< 2.5 x normal limits (grade 1)
- Serum creatinine =< 1.5 x normal limits (grade 1)
- AML (any of the following):
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- Newly diagnosed AML in adults >= 75 years
- Newly diagnosed AML arising from MDS in adults >= 65 years
- Hyperleukocytosis with >= 30,000 leukemic blasts/uL
Who cannot join
- Acute promyelocytic (FAB M3) subtype
- Previously treated with chemotherapy for leukemia (except for hydroxyurea)
- Disseminated intravascular coagulation (laboratory or clinical)
- Active central nervous system leukemia
- Concomitant radiation therapy, chemotherapy, or immunotherapy; previous therapy for another malignancy is permitted, provided that at least 1 month has occurred since patient received any of these treatments
- Intrinsic impaired organ function (as stated above)
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- Symptomatic neuropathy (grade 2 or worse)
- Known allergy to imidazole drugs, such as ketoconazole, miconazole, econazole, teconazole, clotrimazole, fenticonazole, isoconazole, sulconazole, or ticonazole
- Physical or psychiatric conditions that in the estimation of the principal investigator (PI) or designee place the patient at high risk of toxicity or non-compliance, e.g. severe congestive heart failure (CHF), unstable angina, or poorly controlled psychosis
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins University
Baltimore, Maryland, 21287-8936
About this study
Official title: A Phase II Study of Farnesyl Transferase Inhibitor R115777 (Zarnestra) (R115777 ( Zarnestra), Tipifarnib, R115777, NSC #702818) in Elderly Patients With Previously Untreated Poor-Risk Acute Myeloid Leukemia
Tipifarnib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Phase II trial to study the effectiveness of tipifarnib in treating older patients who have previously untreated acute myeloid leukemia
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the complete response rate of R115777 (tipifarnib) in previously untreated acute myeloid leukemia (AML) in (a) elderly patients (age >= 75) and (b) patients (age >= 65) with AML preceded by myelodysplastic syndrome (MDS), using a chronic dosing schedule.
SECONDARY OBJECTIVES:
- To determine progression-free and overall survival in patients with previously untreated AML treated with R115777, using a chronic dosing schedule.
II. To determine the duration of response in patients with previously untreated AML treated with R115777, using a chronic dosing schedule.
III. To determine the effect of R115777 on the phosphorylation of mitogen-activated protein kinase (MAPK) and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PI3K) in leukemic cells.
IV. To determine the effect of R115777 on processing of the farnesylated protein HDJ-2.
- To determine the toxicities of R115777 when given in a chronic dosing schedule.
OUTLINE: This is a multicenter study.
Patients receive oral tipifarnib twice daily on days 1-21. Patients with a complete or partial response, hematologic improvement, or stable disease continue treatment every 29-63 days in the absence of disease progression or unacceptable toxicity. Patients with a complete response after the second course of therapy receive 2 additional courses of therapy.
Patients are followed for survival.
PROJECTED ACCRUAL: A total of 125 patients will be accrued for this study within 11-17 months.
- Conditions
- Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome, Adult Acute Basophilic Leukemia, Adult Acute Eosinophilic Leukemia, Adult Acute Erythroid Leukemia (M6), Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0)
- Being tested
- tipifarnib, laboratory biomarker analysis
- Medical subject headings
- Leukemia, Basophilic, Acute, Leukemia, Eosinophilic, Acute, Leukemia, Erythroblastic, Acute, Leukemia, Megakaryoblastic, Acute, Leukemia, Monocytic, Acute, Leukemia, Myeloid, Acute, Congenital Abnormalities, Leukemia, Myelomonocytic, Acute
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 |
|---|---|---|
| Treatment (tipifarnib) | Experimental | Patients receive oral tipifarnib twice daily on days 1-21. Patients with a complete or partial response, hematologic improvement, or stable disease continue treatment every 29-63 days in the absence of disease progression or unacceptable toxicity. Patients with a complete response after the second course of therapy receive 2 additional courses of therapy. Receives: Drug: tipifarnib; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete remission (CR) rate
CR rates will be calculated with 95% confidence intervals for each age group separately.
Measured: Up to 8 years
Secondary outcomes (4)
Partial remission (PR) rate
Will be estimated by observed proportions and 95% confidence intervals.
Measured: Up to 8 years
Toxicity rates assessed using NCI CTCAE version 3.0
Will be estimated by observed proportions and 95% confidence intervals.
Measured: Up to 8 years
Duration of response
Duration of response and survival will be summarized by the Kaplan-Meier estimate of the survival distribution.
Measured: From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 8 years
Duration of survival
Duration of response and survival will be summarized by the Kaplan-Meier estimate of the survival distribution.
Measured: From time of enrollment onto this study to the time of death, assessed up to 8 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 startOct 2001
- Primary completionJul 2007
- Study completionJan 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic SyndromeStudies 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
- 125 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Judith Karp, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00027872
- Sponsor's protocol ID
- NCI-2012-02980
- Other IDs
- UMGCC 0116, U01CA069854, U01CA070095
- Status last verified
- Mar 2013
- First submitted
- 7 Dec 2001
- Last updated
- 25 Mar 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Farnesyl Transferase Inhibitor R115777 (Zarnestra) (R115777 ( Zarnestra), Tipifarnib, R115777, NSC #702818) in Elderly Patients With Previously Untreated Poor-Risk Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT00027872
- Acronym / sponsor ID
- NCI-2012-02980
- Conditions
- Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome, Adult Acute Basophilic Leukemia, Adult Acute Eosinophilic Leukemia, Adult Acute Erythroid Leukemia (M6), Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 125 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Oct 2001
- Primary completion
- Jul 2007 (actual)
- Study completion
- Jan 2009 (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.
Tipifarnib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Phase II trial to study the effectiveness of tipifarnib in treating older patients who have previously untreated acute myeloid leukemia
Detailed description
PRIMARY OBJECTIVES:
- To determine the complete response rate of R115777 (tipifarnib) in previously untreated acute myeloid leukemia (AML) in (a) elderly patients (age >= 75) and (b) patients (age >= 65) with AML preceded by myelodysplastic syndrome (MDS), using a chronic dosing schedule.
SECONDARY OBJECTIVES:
- To determine progression-free and overall survival in patients with previously untreated AML treated with R115777, using a chronic dosing schedule.
II. To determine the duration of response in patients with previously untreated AML treated with R115777, using a chronic dosing schedule.
III. To determine the effect of R115777 on the phosphorylation of mitogen-activated protein kinase (MAPK) and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PI3K) in leukemic cells.
IV. To determine the effect of R115777 on processing of the farnesylated protein HDJ-2.
- To determine the toxicities of R115777 when given in a chronic dosing schedule.
OUTLINE: This is a multicenter study.
Patients receive oral tipifarnib twice daily on days 1-21. Patients with a complete or partial response, hematologic improvement, or stable disease continue treatment every 29-63 days in the absence of disease progression or unacceptable toxicity. Patients with a complete response after the second course of therapy receive 2 additional courses of therapy.
Patients are followed for survival.
PROJECTED ACCRUAL: A total of 125 patients will be accrued for this study within 11-17 months.
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 analysisPatients receive oral tipifarnib twice daily on days 1-21. Patients with a complete or partial response, hematologic improvement, or stable disease continue treatment every 29-63 days in the absence of disease progression or unacceptable toxicity. Patients with a complete response after the second course of therapy receive 2 additional courses of therapy. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (9 listed)
- Pathologic confirmation of the diagnosis of AML (>= 20% marrow blasts)
- ECOG performance status 0 or 1
- Patients must be able to give informed consent
- SGOT and SGPT =< 2.5 x normal limits (grade 1)
- Serum creatinine =< 1.5 x normal limits (grade 1)
Key exclusion criteria (9 listed)
- Acute promyelocytic (FAB M3) subtype
- Previously treated with chemotherapy for leukemia (except for hydroxyurea)
- Disseminated intravascular coagulation (laboratory or clinical)
- Active central nervous system leukemia
- Concomitant radiation therapy, chemotherapy, or immunotherapy; previous therapy for another malignancy is permitted, provided that at least 1 month has occurred since patient received any of these treatments
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 | Treatment (tipifarnib) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (tipifarnib) |
Primary outcome
Complete remission (CR) rate
Time frame: Up to 8 years
CR rates will be calculated with 95% confidence intervals for each age group separately.
4 secondary outcomes
Partial remission (PR) rate
Time frame: Up to 8 years
Toxicity rates assessed using NCI CTCAE version 3.0
Time frame: Up to 8 years
Duration of response
Time frame: From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 8 years
Duration of survival
Time frame: From time of enrollment onto this study to the time of death, assessed up to 8 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 25 Mar 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.
Judith Karp principal investigator
Johns Hopkins University
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 Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome and Adult Acute Basophilic 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 9 inclusion and 9 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 25 Mar 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?
Complete remission (CR) rate (time frame: Up to 8 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 25 Mar 2013.