Clinical trial · Interventional
Tipifarnib and Etoposide in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia
A Phase I Trial of Oral Etoposide in Combination With the Farnesyltransferase Inhibitor R115777 (ZARNESTRA, Tipifarnib, NSC #702818, IND #58,359) in Elderly Adults With Newly Diagnosed Acute Myelogenous Leukemia (AML)
NCT00112853CI-TRIAL-00008841completedPhase 1ClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
This phase I trial is studying the side effects and best dose of tipifarnib and etoposide in treating older patients with newly diagnosed 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
Conditions
Conditions (15)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Adult Acute Megakaryoblastic Leukemia (M7) | Adult Acute Megakaryoblastic Leukemia | ONTOLOGY_EXACT | 0.85 |
| Adult Acute Minimally Differentiated Myeloid Leukemia (M0) | Adult Acute Myeloid Leukemia with Minimal Differentiation | ALIAS | 0.90 |
| Adult Acute Monoblastic Leukemia (M5a) | Adult Acute Monoblastic Leukemia | ONTOLOGY_EXACT | 0.85 |
| Adult Acute Monocytic Leukemia (M5b) | Adult Acute Monocytic Leukemia | ONTOLOGY_EXACT | 0.85 |
| Adult Acute Myeloblastic Leukemia With Maturation (M2) | Adult Acute Myeloid Leukemia with Maturation | ALIAS | 0.90 |
| Adult Acute Myeloblastic Leukemia Without Maturation (M1) | Adult Acute Myeloid Leukemia without Maturation | ALIAS |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| etoposide | Drug | Etoposide | ALIAS |
| tipifarnib | Drug | Tipifarnib | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Treatment (tipifarnib, etoposide)
- description
- Patients receive oral tipifarnib twice daily on days 1-14 OR 1-21 and oral etoposide once daily on days 1-3 and 8-10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who achieve a CR may receive up to 5 additional courses of therapy beyond documentation of CR. Cohorts of 3-6 patients receive escalating doses of tipifarnib and etoposide until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Up to 14 additional patients receive treatment at the MTD.
- interventionNames
- Drug: tipifarnib
- Drug: etoposide
Primary outcomes (4)
- measure
- Number of patients who experience dose limiting toxicities (DLT), based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0
- timeFrame
- Up to 28 days
- measure
- Clinical response in terms of optimal dose combination for further study
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 70 Years
Show eligibility criteria text
Inclusion Criteria: * Adults age with established, pathologically confirmed diagnoses of newly diagnosed AML, including de novo and secondary AMLs but excluding newly diagnosed acute progranulocytic leukemia (APL, M3), will be considered eligible for study * ECOG performance status 0-2 * Patient must be able to give informed consent * Serum creatinine =\< 2.0 mg/dl * SGOT and SGPT =\< 5 x upper limit normal (ULN) * Bilirubin =\< 2 mg/dl * Disease-specific criteria: * Newly diagnosed AML, subtypes M0,1,2,4-7 but excluding M3 (APL), including myelodysplasia (MDS)-related AML (MDS/AML) and treatment-related AML * Patients who have received hydroxyurea alone or have received non-cytotoxic therapies previously for MDS (e.g., thalidomide, interferon, cytokines, 5-azacytidine) will be eligible for this trial Exclusion Criteria: * Any previous treatment with R115777 or VP-16 * Patients receiving concomitant chemotherapy, radiation therapy or immunotherapy * Hyperleukocytosis with \>= 30,000 blasts/uL or rapidly rising blast count with projected doubling time of =\< 2 days * Acute progranulocytic leukemia (APL,M3) * Active CNS leukemia * Active, uncontrolled infection; patients with infection under active treatment and controlled with antibiotics are eligible * Presence of other life-threatening illness * Patients with mental deficits and/or psychiatric history that preclude them from giving informed consent or from following protocol * Patients on enzyme-inducing anti-convulsants (e.g., phenytoin, fosphenytoin, phenobarbital, primidone, carbamazepine, oxcarbazepine); patients may be changed to non-enzyme inducing anti-convulsants and stabilized before starting study treatment
References
Publications (1)
- DERIVEDKarp JE, Flatten K, Feldman EJ, Greer JM, Loegering DA, Ricklis RM, Morris LE, Ritchie E, Smith BD, Ironside V, Talbott T, Roboz G, Le SB, Meng XW, Schneider PA, Dai NT, Adjei AA, Gore SD, Levis MJ, Wright JJ, Garrett-Mayer E, Kaufmann SH. Active oral regimen for elderly adults with newly diagnosed acute myelogenous leukemia: a preclinical and phase 1 trial of the farnesyltransferase inhibitor tipifarnib (R115777, Zarnestra) combined with etoposide. Blood. 2009 May 14;113(20):4841-52. doi: 10.1182/blood-2008-08-172726. Epub 2008 Dec 24. PMID 19109557