Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic SyndromePhase 2NCT00602771
Tipifarnib and Etoposide in Treating Older Patients With Newly Diagnosed, Previously Untreated Acute Myeloid Leukemia
A Phase 2 study testing tipifarnib and etoposide in people with Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome and Adult Acute Megakaryoblastic Leukemia (M7), run by National Cancer Institute (NCI) at 5 sites in United States.
Trial summary
This randomized phase II trial is studying the side effects and how well giving tipifarnib together with etoposide works in treating older patients with newly diagnosed, previously untreated acute myeloid leukemia. 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 70 years and older
- Conditions the study is for
- Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome, Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0)
- What is being tested?
- tipifarnib and etoposide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 84 participants
- Where
- 5 sitesUnited States
- Study dates
- Jan 2008to Oct 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- ECOG performance status 0-2
- Serum creatinine =< 2.0 mg/dL
- SGOT and SGPT =< 3 times upper limit of normal
- Bilirubin =< 2 mg/dL
Who cannot join
- Active, uncontrolled infection
- Patients with infection under active treatment and controlled with antimicrobials are eligible
- Presence of other life-threatening illnesses
- Patients with mental deficits and/or psychiatric history that preclude them from giving informed consent or from following protocol
- Allergies to imidazoles (e.g., clotrimazole, ketoconazole, miconazole, or econazole)
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
University of Michigan
Ann Arbor, Michigan, 48109
Blood and Marrow Transplant Group of Georgia
Atlanta, Georgia, 30342
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Weill Medical College of Cornell University
New York, New York, 10065
Mayo Clinic
Rochester, Minnesota, 55905
About this study
Official title: A Randomized Phase II Trial of Tipifarnib (R115777, ZARNESTRA, NSC #702818) in Combination With Oral Etoposide (VP-16) in Elderly Adults With Newly Diagnosed, Previously Untreated Acute Myelogenous Leukemia (AML)
This randomized phase II trial is studying the side effects and how well giving tipifarnib together with etoposide works in treating older patients with newly diagnosed, previously untreated acute myeloid leukemia. Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving tipifarnib together with etoposide may kill more cancer cells.
Read the detailed description
OBJECTIVES:
- To compare the efficacy and toxicity of two schedules of tipifarnib plus etoposide as induction therapy in older patients with newly diagnosed, previously untreated acute myeloid leukemia.
II. To study mechanisms of leukemia cell resistance to tipifarnib in combination with etoposide.
OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive 600 mg of oral tipifarnib twice daily on days 1-14 and 100 mg of oral etoposide once daily on days 1-3 and 8-10.
ARM II: Patients receive 400 mg of oral tipifarnib twice daily on days 1-14 and 200 mg of oral etoposide once daily on days 1-3 and 8-10. (closed to accrual as of November 2008)
Treatment in both arms repeats every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed at 30 days and then every 90 days thereafter.
- Conditions
- Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome, 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)
- Being tested
- tipifarnib, etoposide
- 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
etoposideDrug
Also called EPEG, VP-16, VP-16-213
Given orally
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | Patients receive 600 mg of oral tipifarnib twice daily on days 1-14 and 100 mg of oral etoposide once daily on days 1-3 and 8-10. Receives: Drug: tipifarnib; Drug: etoposide |
| Arm II (closed to accrual as of November 2008) | Experimental | Patients receive 400 mg of oral tipifarnib twice daily on days 1-14 and 200 mg of oral etoposide once daily on days 1-3 and 8-10. Receives: Drug: tipifarnib; Drug: etoposide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Response
Bone marrow showing less than 5% myeloblasts with normal maturation of all cell lines, an ANC of at least 1000/mcL and a platelet count of 100,000 mcL, absence of blast in peripheral blood, absence of identifiable leukemic cells in the bone marrow, clearance of disease-associated cytogenetic abnormalities, and clearance of any previously existing extramedullary disease. A CR must be confirmed 4 to 6 weeks after the initial documentation. If possible, at least one bone marrow biopsy should be performed to confirm the CR.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2008 (estimated)
- Study startJan 2008
- Primary completionOct 2011
- Study completionOct 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 84 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/Sidney Kimmel Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00602771
- Sponsor's protocol ID
- NCI-2009-00278
- Other IDs
- NCI-2009-00278, CDR0000584212, J07109, 8077, N01CM62204, P30CA006973, U01CA070095
- Status last verified
- Jun 2014
- First submitted
- 19 Jan 2008
- Last updated
- 9 Oct 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Ding H, McDonald JS, Yun S, Schneider PA, Peterson KL, Flatten KS, Loegering DA, Oberg AL, Riska SM, Huang S, Sinicrope FA, Adjei AA, Karp JE, Meng XW, Kaufmann SH. Farnesyltransferase inhibitor tipifarnib inhibits Rheb prenylation and stabilizes Bax in acute myelogenous leukemia cells. Haematologica. 2014 Jan;99(1):60-9. doi: 10.3324/haematol.2013.087734. Epub 2013 Aug 30.
PubMed 23996484Karp JE, Vener TI, Raponi M, Ritchie EK, Smith BD, Gore SD, Morris LE, Feldman EJ, Greer JM, Malek S, Carraway HE, Ironside V, Galkin S, Levis MJ, McDevitt MA, Roboz GR, Gocke CD, Derecho C, Palma J, Wang Y, Kaufmann SH, Wright JJ, Garret-Mayer E. Multi-institutional phase 2 clinical and pharmacogenomic trial of tipifarnib plus etoposide for elderly adults with newly diagnosed acute myelogenous leukemia. Blood. 2012 Jan 5;119(1):55-63. doi: 10.1182/blood-2011-08-370825. Epub 2011 Oct 14.
PubMed 22001391
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase II Trial of Tipifarnib (R115777, ZARNESTRA, NSC #702818) in Combination With Oral Etoposide (VP-16) in Elderly Adults With Newly Diagnosed, Previously Untreated Acute Myelogenous Leukemia (AML)
- ClinicalTrials.gov ID
- NCT00602771
- Acronym / sponsor ID
- NCI-2009-00278
- Conditions
- Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome, 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)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 84 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jan 2008
- Primary completion
- Oct 2011 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 28 Jan 2008 (estimated)
- Results
- Posted 26 May 2014
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 the side effects and how well giving tipifarnib together with etoposide works in treating older patients with newly diagnosed, previously untreated acute myeloid leukemia. Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving tipifarnib together with etoposide may kill more cancer cells.
Detailed description
OBJECTIVES:
- To compare the efficacy and toxicity of two schedules of tipifarnib plus etoposide as induction therapy in older patients with newly diagnosed, previously untreated acute myeloid leukemia.
II. To study mechanisms of leukemia cell resistance to tipifarnib in combination with etoposide.
OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive 600 mg of oral tipifarnib twice daily on days 1-14 and 100 mg of oral etoposide once daily on days 1-3 and 8-10.
ARM II: Patients receive 400 mg of oral tipifarnib twice daily on days 1-14 and 200 mg of oral etoposide once daily on days 1-3 and 8-10. (closed to accrual as of November 2008)
Treatment in both arms repeats every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed at 30 days and then every 90 days thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Drug: tipifarnib, Drug: etoposidePatients receive 600 mg of oral tipifarnib twice daily on days 1-14 and 100 mg of oral etoposide once daily on days 1-3 and 8-10. |
| Arm II (closed to accrual as of November 2008) | Experimental | Drug: tipifarnib, Drug: etoposidePatients receive 400 mg of oral tipifarnib twice daily on days 1-14 and 200 mg of oral etoposide once daily on days 1-3 and 8-10. |
Who may qualify
- Ages
- 70 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (4 listed)
- ECOG performance status 0-2
- Serum creatinine =< 2.0 mg/dL
- SGOT and SGPT =< 3 times upper limit of normal
- Bilirubin =< 2 mg/dL
Key exclusion criteria (5 listed)
- Active, uncontrolled infection
- Patients with infection under active treatment and controlled with antimicrobials are eligible
- Presence of other life-threatening illnesses
- Patients with mental deficits and/or psychiatric history that preclude them from giving informed consent or from following protocol
- Allergies to imidazoles (e.g., clotrimazole, ketoconazole, miconazole, or econazole)
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 (closed to accrual as of November 2008) |
| etoposideAlso: EPEG, VP-16, VP-16-213Given orally | Drug | Arm I, Arm II (closed to accrual as of November 2008) |
Primary outcome
Complete Response
Time frame: 6 months
Bone marrow showing less than 5% myeloblasts with normal maturation of all cell lines, an ANC of at least 1000/mcL and a platelet count of 100,000 mcL, absence of blast in peripheral blood, absence of identifiable leukemic cells in the bone marrow, clearance of disease-associated cytogenetic abnormalities, and clearance of any previously existing extramedullary disease. A CR must be confirmed 4 to 6 weeks after the initial documentation. If possible, at least one bone marrow biopsy should be performed to confirm the CR.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23996484Ding H, McDonald JS, Yun S, Schneider PA, Peterson KL, Flatten KS, Loegering DA, Oberg AL, Riska SM, Huang S, Sinicrope FA, Adjei AA, Karp JE, Meng XW, Kaufmann SH. Farnesyltransferase inhibitor tipifarnib inhibits Rheb prenylation and stabilizes Bax in acute myelogenous leukemia cells. Haematologica. 2014 Jan;99(1):60-9. doi: 10.3324/haematol.2013.087734. Epub 2013 Aug 30.
- Derived from this study: PubMed 22001391Karp JE, Vener TI, Raponi M, Ritchie EK, Smith BD, Gore SD, Morris LE, Feldman EJ, Greer JM, Malek S, Carraway HE, Ironside V, Galkin S, Levis MJ, McDevitt MA, Roboz GR, Gocke CD, Derecho C, Palma J, Wang Y, Kaufmann SH, Wright JJ, Garret-Mayer E. Multi-institutional phase 2 clinical and pharmacogenomic trial of tipifarnib plus etoposide for elderly adults with newly diagnosed acute myelogenous leukemia. Blood. 2012 Jan 5;119(1):55-63. doi: 10.1182/blood-2011-08-370825. Epub 2011 Oct 14.
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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/Sidney Kimmel Cancer Center
5 sites 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 etoposide in people with Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome and Adult Acute Megakaryoblastic Leukemia (M7), run by National Cancer Institute (NCI) at 5 sites 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 4 inclusion and 5 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 9 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites 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?
Yes. Results are posted in the registry (first posted 26 May 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 Response (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00602771, which also lists 2 linked publications.
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 9 Oct 2014.