Clinical Trial: Combination Chemotherapy and Tipifarnib in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

This study is not yet open for patient recruitment.
Verified by National Cancer Institute (NCI) July 2005

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

MedlinePlus related topics:  Bone Marrow Diseases;   Immune System and Disorders;   Leukemia, Adult Acute;   Leukemia, Adult Chronic;   Leukemia, Childhood;   Lymphatic Diseases

Study Type: Interventional
Study Design: Treatment

Official Title: Phase I Study of Induction Therapy Comprising Cytarabine, Daunorubicin, and Etoposide in Combination With Tipifarnib Followed By Consolidation Therapy Comprising High-Dose Cytarabine in Patients With Newly Diagnosed High-Risk Acute Myeloid Leukemia

Further Study Details: 

OBJECTIVES: Primary

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.

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   -   59 Years,  Genders Eligible for Study:  Both
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

Location and Contact Information

Please refer to this study by ClinicalTrials.gov identifier  NCT00124644


Study chairs or principal investigators

William G. Blum, MD,  Principal Investigator,  Arthur G. James Cancer Hospital & Richard J. Solove Research Institute   

More Information

Clinical trial summary from the National Cancer Institute''''s PDQ® database

Study ID Numbers:  CDR0000437105; OSU-05020; OSU-2005C0024; NCI-6623
Last Updated:  August 1, 2005
Record first received:  July 27, 2005
ClinicalTrials.gov Identifier:  NCT00124644
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-08-02



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