Combination Chemotherapy and Tipifarnib in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia - Full Text View

Sponsors and Collaborators:	Arthur G. James Cancer Hospital & Richard J. Solove Research Institute National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00124644

Purpose

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.

Condition	Intervention	Phase
Leukemia	Drug: cytarabine Drug: daunorubicin hydrochloride Drug: etoposide Drug: tipifarnib Procedure: chemotherapy Procedure: enzyme inhibitor therapy Procedure: high-dose chemotherapy	Phase I

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Cytarabine hydrochloride Daunorubicin Daunorubicin hydrochloride Etoposide R 115777 Tipifarnib Cytarabine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase I Study of R115777 (Zarnestra) in Combination With Induction Chemotherapy in Patients With Newly Diagnosed, High Risk Acute Myeloid Leukemia

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment:	30
Study Start Date:	March 2006
Primary Completion Date:	December 2007 (Final data collection date for primary outcome measure)

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.

Eligibility

Ages Eligible for Study:	18 Years to 59 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00124644

Locations

United States, Ohio
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
Columbus, Ohio, United States, 43210-1240

Sponsors and Collaborators

Arthur G. James Cancer Hospital & Richard J. Solove Research Institute

National Cancer Institute (NCI)

Investigators

Principal Investigator:

William G. Blum, MD

Arthur G. James Cancer Hospital & Richard J. Solove Research Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000437105, OSU-05020, OSU-2005C0024, NCI-6623
Study First Received:	July 26, 2005
Last Updated:	February 20, 2008
ClinicalTrials.gov Identifier:	NCT00124644 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with t(16;16)(p13;q22)
untreated adult acute myeloid leukemia
secondary acute myeloid leukemia

Study placed in the following topic categories:

Antimetabolites
Daunorubicin
Immunologic Factors
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Immunosuppressive Agents
Antiviral Agents
Etoposide phosphate
Leukemia

Anti-Bacterial Agents
Acute Myelocytic Leukemia
Acute Myeloid Leukemia, Adult
Neoplasm Metastasis
Congenital Abnormalities
Etoposide
Cytarabine
Tipifarnib

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Daunorubicin
Antimetabolites, Antineoplastic
Neoplasms by Histologic Type
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Leukemia, Myeloid

Leukemia, Myeloid, Acute
Antibiotics, Antineoplastic
Immunosuppressive Agents
Antiviral Agents
Pharmacologic Actions
Leukemia
Neoplasms
Therapeutic Uses
Cytarabine
Tipifarnib

ClinicalTrials.gov processed this record on May 06, 2009