Adult Acute Megakaryoblastic Leukemia (M7)Phase 2NCT00093418
S0432 Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia
A Phase 2 study testing tipifarnib in people with Adult Acute Megakaryoblastic Leukemia (M7) and Adult Acute Minimally Differentiated Myeloid Leukemia (M0), run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This randomized phase II trial is studying 4 different tipifarnib regimens to compare how well they work in treating older patients with acute myeloid leukemia. Tipifarnib may stop the growth of cancer cells by blocking the enzymes necessary for their growth Read more about this study
- Who is it for?
- Ages 70 years and older
- Conditions the study is for
- Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a)
- What is being tested?
- tipifarnib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 296 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2004to Jun 2006
- 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 70 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Patients must have a morphologically confirmed diagnosis of acute myeloid leukemia (AML) with classification other than WHO Acute Promyelocytic Leukemia (FAB M3), based on bone marrow aspiration and biopsy performed within 14 days prior to registration; if a diagnostic biopsy has been performed within 28 days prior to registration, the marrow blast percentage is >= 70%, and no potentially anti-leukemic therapy has been given in the interim, then this bone marrow examination can be used for registration purposes; Note: This protocol uses the WHO diagnostic criteria for AML, not the FAB criteria; patients with WHO Acute Promyelocytic Leukemia (FAB M3) or blastic transformation of chronic myelogenous leukemia are not eligible; patients must not be candidates for or must have refused standard AML cytotoxic chemotherapy regimens
- Patients must not have received prior systemic chemotherapy for acute leukemia with the exception of hydroxyurea; patients must have a WBC =< 30,000/cmm within 1 day prior to registration; administration of hydroxyurea to control high WBC count prior to, during and after registration is permitted; patients with a history of prior myelodysplastic syndrome are eligible; however, prior treatment with AML induction type chemotherapy or high dose chemotherapy with hematopoietic stem cell support is not allowed; patients may have received hematopoietic growth factors, thalidomide, arsenic trioxide, signal transduction inhibitors, azacitidine, and low dose cytarabine for treatment of myelodysplastic syndrome; however, the dose of cytarabine must be < 100 mg/M2/day; other low intensity therapies for MDS will also be permitted and should be discussed with the Study Coordinator; patients must be off prior therapy for MDS (excluding growth factors) and all toxicities must have resolved; if indicated, a single dose of intrathecal chemotherapy may also be given before or concurrent with induction chemotherapy
- Patient must have a bilirubin =< 1.5 x Institutional Upper Limit of Normal (IULN), unless the elevation is due primarily to elevated unconjugated hyperbilirubinemia secondary to Gilbert's syndrome or hemolysis and not to liver dysfunction
- SGOT (AST) =< 2.5 x IULN, or SGPT (ALT) =< 2.5 x IULN, or both within 14 days prior to registration
- Patients must have a serum creatinine =< 1.5 x IULN within 14 days prior to registration
- Southwest Oncology Group patients must be registered on SWOG-9007, the cytogenetics protocol; collection of pretreatment marrow specimens must be completed within 14 days prior to registration; pretreatment specimens of bone marrow must be submitted to an approved Southwest Oncology Group Cytogenetics Laboratory for cytogenetic analysis; note that protocol SWOG-9007 also requires submission of remission and relapse specimens
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- ECOG and CALGB have similar cytogenetics studies; please check with your group to find out about requirements for participation; CTSU sites will not be participating in SWOG-9007 and will not be submitting specimens for this study
- All patients must have cytogenetics performed and - if not registered to SWOG-9007 - a cytogenetics report submitted to the Cytogenetics Office at the Southwest Oncology Group Data Operations Center
- Southwest Oncology Group patients must be offered participation in S9910, the leukemia centralized reference laboratories and tissue repositories ancillary study; if consent is given, collection of pretreatment blood and/or marrow specimens must be completed within 14 days prior to registration; if the patient consents to participate in S9910, pretreatment specimens of marrow and/or peripheral blood must be submitted to the Southwest Oncology Group Myeloid Repository at the University of New Mexico for cellular and molecular studies; S9910 also requests submission of remission and relapse specimens
- ECOG and CALGB have similar reference laboratories and repository protocols; please check with your group to find out about requirements for participation
- CTSU sites will not be participating in S9910 and will not be submitting specimens for this study
- Patients of reproductive potential must have agreed to use an effective contraceptive method
- Patients with a prior malignancy are eligible; however, the patient must have completed all chemotherapy and radiotherapy at least 6 months prior to study registration; there should be no plan to begin therapy for the prior malignancy at the time of study registration; concurrent hormonal therapy is allowed
- Patients who are expected to require treatment with enzyme inducing antiepileptic drugs (EIAED) are not eligible for this study
- If day 14 or 30 falls on a weekend or holiday, the limit may be extended to the next working day; in calculating days of tests and measurements, the day a test or measurement is done is considered Day 0; therefore, if a test is done on a Monday, the Monday two weeks later would be considered Day 14; this allows for efficient patient scheduling without exceeding the guidelines
- All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
- At the time of patient registration, the treating institution's name and ID number must be provided to the Data Operations Center in Seattle in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the data base
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Studies of Two Different Schedules and Two Different Doses of the Farnesyl Transferase Inhibitor R115777 (Tipifarnib, Zarnestra®, NSC-702818) for Previously Untreated Acute Myeloid Leukemia (AML) in Patients of Age 70 or Older
This randomized phase II trial is studying 4 different tipifarnib regimens to compare how well they work in treating older patients with acute myeloid leukemia. Tipifarnib may stop the growth of cancer cells by blocking the enzymes necessary for their growth
Read the detailed description
PRIMARY OBJECTIVES:
- To test whether any or all of four different regimens of R115777 (tipifarnib) is sufficiently effective therapy for previously untreated acute myeloid leukemia (AML) in patients of age 70 or older to warrant Phase III investigation. Additionally, to allow increased access for patients to an agent that appears promising in this patient population.
II. To estimate the frequency and severity of toxicities of these regimens in this group of patients.
III. To investigate in a preliminary manner the relationship of cytogenetics with response to R115777 (tipifarnib) and assess whether karyotype represents a potential prognostic factor among older AML patients who are not candidates for chemotherapy and are treated with R1157777.
IV. To collect specimens for future correlations (e.g. RAS and downstream targets) to be identified at a later date.
OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 4 treatment arms.
ARM I: Patients receive oral tipifarnib twice daily on days 1-21. ARM II: Patients receive oral tipifarnib twice daily on days 1-7 and 15-21. ARM III: Patients receive tipifarnib as in arm I, but at a lower dose. ARM IV: Patients receive tipifarnib as in arm II, but at a lower dose.
In all arms, courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Patients who achieve a complete remission (CR) receive up to 3 additional courses beyond CR. Patients in CR who develop recurrent disease after the completion of therapy are eligible to receive tipifarnib again.
Patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually for 3 years.
- Conditions
- Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b), Adult Acute Myeloblastic Leukemia With Maturation (M2), Adult Acute Myeloblastic Leukemia Without Maturation (M1)
- Being tested
- tipifarnib
- Medical subject headings
- Leukemia, Megakaryoblastic, Acute, Leukemia, Monocytic, Acute, Leukemia, Myeloid, Acute, Congenital Abnormalities, Leukemia, Myelomonocytic, Acute, Leukemia, Erythroblastic, 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
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | Arm I: Patients receive oral tipifarnib twice daily on days 1-21. In all arms, courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Patients who achieve a complete remission (CR) receive up to 3 additional courses beyond CR. Patients in CR who develop recurrent disease after the completion of therapy are eligible to receive tipifarnib again. Receives: Drug: tipifarnib |
| Arm II | Experimental | Patients receive oral tipifarnib twice daily on days 1-7 and 15-21. In all arms, courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Patients who achieve a complete remission (CR) receive up to 3 additional courses beyond CR. Patients in CR who develop recurrent disease after the completion of therapy are eligible to receive tipifarnib again. Receives: Drug: tipifarnib |
| Arm III | Experimental | Patients receive tipifarnib as in arm I, but at a lower dose. In all arms, courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Patients who achieve a complete remission (CR) receive up to 3 additional courses beyond CR. Patients in CR who develop recurrent disease after the completion of therapy are eligible to receive tipifarnib again. Receives: Drug: tipifarnib |
| Arm IV | Experimental | Patients receive tipifarnib as in arm II, but at a lower dose. In all arms, courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Patients who achieve a complete remission (CR) receive up to 3 additional courses beyond CR. Patients in CR who develop recurrent disease after the completion of therapy are eligible to receive tipifarnib again. Receives: Drug: tipifarnib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total response rate, defined as the proportion of patients who achieve CR or PR
Any of the regimens considered in this trial would be considered sufficiently promising for further study if it increased the true total response rate of 30%, but not sufficiently promising if it produced a true total response rate of only 10%.
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2004 (estimated)
- Study startSep 2004
- Primary completionJun 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adult Acute Megakaryoblastic Leukemia (M7)Studies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 296 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Harry Erba, Principal investigator, SWOG Cancer Research Network
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00093418
- Sponsor's protocol ID
- NCI-2012-03038
- Other IDs
- S0432, U10CA032102, CDR0000387957
- Status last verified
- Jan 2013
- First submitted
- 6 Oct 2004
- Last updated
- 15 Jan 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Studies of Two Different Schedules and Two Different Doses of the Farnesyl Transferase Inhibitor R115777 (Tipifarnib, Zarnestra®, NSC-702818) for Previously Untreated Acute Myeloid Leukemia (AML) in Patients of Age 70 or Older
- ClinicalTrials.gov ID
- NCT00093418
- Acronym / sponsor ID
- NCI-2012-03038
- Conditions
- Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b), Adult Acute Myeloblastic Leukemia With Maturation (M2), Adult Acute Myeloblastic Leukemia Without Maturation (M1)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 296 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Sep 2004
- Primary completion
- Jun 2006 (actual)
- First posted
- 8 Oct 2004 (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 randomized phase II trial is studying 4 different tipifarnib regimens to compare how well they work in treating older patients with acute myeloid leukemia. Tipifarnib may stop the growth of cancer cells by blocking the enzymes necessary for their growth
Detailed description
PRIMARY OBJECTIVES:
- To test whether any or all of four different regimens of R115777 (tipifarnib) is sufficiently effective therapy for previously untreated acute myeloid leukemia (AML) in patients of age 70 or older to warrant Phase III investigation. Additionally, to allow increased access for patients to an agent that appears promising in this patient population.
II. To estimate the frequency and severity of toxicities of these regimens in this group of patients.
III. To investigate in a preliminary manner the relationship of cytogenetics with response to R115777 (tipifarnib) and assess whether karyotype represents a potential prognostic factor among older AML patients who are not candidates for chemotherapy and are treated with R1157777.
IV. To collect specimens for future correlations (e.g. RAS and downstream targets) to be identified at a later date.
OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 4 treatment arms.
ARM I: Patients receive oral tipifarnib twice daily on days 1-21. ARM II: Patients receive oral tipifarnib twice daily on days 1-7 and 15-21. ARM III: Patients receive tipifarnib as in arm I, but at a lower dose. ARM IV: Patients receive tipifarnib as in arm II, but at a lower dose.
In all arms, courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Patients who achieve a complete remission (CR) receive up to 3 additional courses beyond CR. Patients in CR who develop recurrent disease after the completion of therapy are eligible to receive tipifarnib again.
Patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually for 3 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Drug: tipifarnibArm I: Patients receive oral tipifarnib twice daily on days 1-21. In all arms, courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Patients who achieve a complete remission (CR) receive up to 3 additional courses beyond CR. Patients in CR who develop recurrent disease after the completion of therapy are eligible to receive tipifarnib again. |
| Arm II | Experimental | Drug: tipifarnibPatients receive oral tipifarnib twice daily on days 1-7 and 15-21. In all arms, courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Patients who achieve a complete remission (CR) receive up to 3 additional courses beyond CR. Patients in CR who develop recurrent disease after the completion of therapy are eligible to receive tipifarnib again. |
| Arm III | Experimental | Drug: tipifarnibPatients receive tipifarnib as in arm I, but at a lower dose. In all arms, courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Patients who achieve a complete remission (CR) receive up to 3 additional courses beyond CR. Patients in CR who develop recurrent disease after the completion of therapy are eligible to receive tipifarnib again. |
| Arm IV | Experimental | Drug: tipifarnibPatients receive tipifarnib as in arm II, but at a lower dose. In all arms, courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Patients who achieve a complete remission (CR) receive up to 3 additional courses beyond CR. Patients in CR who develop recurrent disease after the completion of therapy are eligible to receive tipifarnib again. |
Who may qualify
- Ages
- 70 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (17 listed)
- Patients must have a morphologically confirmed diagnosis of acute myeloid leukemia (AML) with classification other than WHO Acute Promyelocytic Leukemia (FAB M3), based on bone marrow aspiration and biopsy performed within 14 days prior to registration; if a diagnostic biopsy has been performed within 28 days prior to registration, the marrow blast percentage is >= 70%, and no potentially anti-leukemic therapy has been given in the interim, then this bone marrow examination can be used for registration purposes; Note: This protocol uses the WHO diagnostic criteria for AML, not the FAB criteria; patients with WHO Acute Promyelocytic Leukemia (FAB M3) or blastic transformation of chronic myelogenous leukemia are not eligible; patients must not be candidates for or must have refused standard AML cytotoxic chemotherapy regimens
- Patients must not have received prior systemic chemotherapy for acute leukemia with the exception of hydroxyurea; patients must have a WBC =< 30,000/cmm within 1 day prior to registration; administration of hydroxyurea to control high WBC count prior to, during and after registration is permitted; patients with a history of prior myelodysplastic syndrome are eligible; however, prior treatment with AML induction type chemotherapy or high dose chemotherapy with hematopoietic stem cell support is not allowed; patients may have received hematopoietic growth factors, thalidomide, arsenic trioxide, signal transduction inhibitors, azacitidine, and low dose cytarabine for treatment of myelodysplastic syndrome; however, the dose of cytarabine must be < 100 mg/M2/day; other low intensity therapies for MDS will also be permitted and should be discussed with the Study Coordinator; patients must be off prior therapy for MDS (excluding growth factors) and all toxicities must have resolved; if indicated, a single dose of intrathecal chemotherapy may also be given before or concurrent with induction chemotherapy
- Patient must have a bilirubin =< 1.5 x Institutional Upper Limit of Normal (IULN), unless the elevation is due primarily to elevated unconjugated hyperbilirubinemia secondary to Gilbert's syndrome or hemolysis and not to liver dysfunction
- SGOT (AST) =< 2.5 x IULN, or SGPT (ALT) =< 2.5 x IULN, or both within 14 days prior to registration
- Patients must have a serum creatinine =< 1.5 x IULN within 14 days prior to registration
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 |
|---|---|---|
| tipifarnibAlso: R115777, ZarnestraGiven orally | Drug | Arm I, Arm II, Arm III, Arm IV |
Primary outcome
Total response rate, defined as the proportion of patients who achieve CR or PR
Time frame: Up to 3 years
Any of the regimens considered in this trial would be considered sufficiently promising for further study if it increased the true total response rate of 30%, but not sufficiently promising if it produced a true total response rate of only 10%.
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 Jan 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.
Harry Erba principal investigator
SWOG Cancer Research Network
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 in people with Adult Acute Megakaryoblastic Leukemia (M7) and Adult Acute Minimally Differentiated Myeloid Leukemia (M0), 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 17 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 Jan 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?
Total response rate, defined as the proportion of patients who achieve CR or PR (time frame: Up to 3 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 15 Jan 2013.