- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00124644
Combination Chemotherapy and Tipifarnib in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
A Phase I Study of R115777 (Zarnestra) in Combination With Induction Chemotherapy in Patients With Newly Diagnosed, High Risk Acute Myeloid Leukemia
RATIONALE: Drugs used in chemotherapy, such as cytarabine, daunorubicin, and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy together with tipifarnib may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of tipifarnib when given together with combination chemotherapy in treating patients with newly diagnosed acute myeloid leukemia.
Study Overview
Status
Conditions
Detailed Description
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of tipifarnib when given in combination with induction therapy comprising cytarabine, daunorubicin, and etoposide followed by consolidation therapy comprising high-dose cytarabine in patients with newly diagnosed high-risk acute myeloid leukemia.
Secondary
- Determine the qualitative and quantitative toxic effects of this regimen, in terms of organ specificity, time course, predictability, and reversibility, in these patients.
- Determine the rate of complete remission in patients treated with this regimen.
- Determine the remission duration, overall survival, and relapse-free and event-free survival of patients treated with this regimen.
- Determine the pharmacokinetics of this regimen in these patients.
- Correlate pharmacodynamic measurements and levels of tumor necrosis factor-alpha with clinical response in patients treated with this regimen.
OUTLINE: This is a dose-escalation study of tipifarnib.
- Induction therapy: Patients receive cytarabine IV continuously on days 1-7; daunorubicin IV and etoposide IV over 2 hours on days 5-7; and oral tipifarnib twice daily on days 5-12.
Patients undergo bone marrow biopsy on day 17 OR days 17 and 24 (if day 17 bone marrow biopsy shows suspicious disease). Patients achieving a complete remission (CR) proceed to consolidation therapy. Patients with residual disease, defined as > 5% leukemic blasts in a bone marrow of ≥ 20% cellularity, receive a second course of induction therapy comprising cytarabine IV continuously on days 1-5; daunorubicin IV and etoposide IV over 2 hours on days 4 and 5; and oral tipifarnib twice daily on days 4-9. Patients achieving a CR after a second course of induction therapy proceed to consolidation therapy. Patients not achieving a CR after a second course of induction therapy are removed from the study.
Cohorts of 3-6 patients receive escalating doses of tipifarnib until the maximum tolerated dose (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. An additional 12 patients are treated at the MTD.
- Consolidation therapy: Patients receive high-dose cytarabine IV twice daily on days 1, 3, and 5. Treatment repeats approximately every 6-8 weeks for 4 courses.
After completion of study treatment, patients are followed every 3-6 months for up to 5 years.
PROJECTED ACCRUAL: A maximum of 30 patients will be accrued for this study within 10-15 months.
Study Type
Enrollment
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Ohio
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Columbus, Ohio, United States, 43210-1240
- Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed acute myeloid leukemia (AML) according to the WHO classification system
- High-risk disease
- Newly diagnosed disease
- Patients with secondary AML due to prior chemotherapy for a different malignancy are eligible
- No known inv(16), t(8;21), or t(15;17) cytogenetic abnormality
- No acute promyelocytic leukemia
- No CNS leukemia
PATIENT CHARACTERISTICS:
Age
- 18 to 59
Performance status
- ECOG 0-2
Life expectancy
- More than 6 months
Hematopoietic
- Not specified
Hepatic
- AST and ALT ≤ 2.5 times upper limit of normal
- Bilirubin normal
Renal
- Creatinine normal OR
- Creatinine clearance ≥ 60 mL/min
Cardiovascular
- Ejection fraction > 50% by echocardiogram or MUGA
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
Immunologic
- No known HIV positivity
- No history of allergic reactions attributed to compounds of similar chemical or biological composition to tipifarnib
- No allergy to imidazoles (e.g., clotrimazole, ketoconazole, miconazole, or econazole)
- No ongoing or active infection
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No other uncontrolled illness
- No psychiatric illness or social situation that would preclude study compliance
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No concurrent epoetin alfa
Chemotherapy
- See Disease Characteristics
- No prior chemotherapy for AML or myelodysplastic syndromes except hydroxyurea
Endocrine therapy
- Not specified
Radiotherapy
- No concurrent palliative radiotherapy
Surgery
- Not specified
Other
- More than 30 days since prior investigational agents
- No other concurrent investigational or commercial agents or therapies for the malignancy
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: William G. Blum, MD, Ohio State University Comprehensive Cancer Center
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Antibiotics, Antineoplastic
- Etoposide
- Cytarabine
- Daunorubicin
- Tipifarnib
- Enzyme Inhibitors
Other Study ID Numbers
- CDR0000437105
- OSU-05020
- OSU-2005C0024
- NCI-6623
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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