Tipifarnib and Etoposide in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia - Full Text View

Sponsors and Collaborators:	Sidney Kimmel Comprehensive Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00112853

Purpose

RATIONALE: 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.

PURPOSE: 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.

Condition	Intervention	Phase
Leukemia	Drug: etoposide Drug: tipifarnib	Phase I

Study Type:	Interventional
Study Design:	Treatment
Official Title:	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)

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Etoposide Etoposide phosphate R 115777 Tipifarnib

U.S. FDA Resources

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

Estimated Enrollment:	100
Study Start Date:	March 2005
Primary Completion Date:	May 2009 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Determine the feasibility, tolerability, and toxic effects of tipifarnib and etoposide in older patients with newly diagnosed, previously untreated acute myeloid leukemia.
Determine the maximum tolerated dose of this regimen in these patients.

OUTLINE: This is a multicenter, dose-escalation study.

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 complete response (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 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. Up to 14 additional patients receive treatment at the MTD.

After completion of study treatment, patients are followed at 1 month and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 3-100 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	70 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed acute myeloid leukemia (AML), including the following subtypes:
- M0
- M1
- M2
- M4
- M5
- M6
- M7
Newly diagnosed de novo or secondary (myelodysplastic syndrome [MDS]-related or treatment-related) AML
No hyperleukocytosis (i.e., ≥ 30,000 blasts/μL or rapidly rising blast count with projected doubling time of ≤ 2 days)
No acute promyelocytic leukemia (M3)
No active CNS leukemia

PATIENT CHARACTERISTICS:

Age

70 and over

Performance status

ECOG 0-2

Life expectancy

Not specified

Hematopoietic

See Disease Characteristics

Hepatic

SGOT and SGPT ≤ 5 times upper limit of normal
Bilirubin ≤ 2.0 mg/dL

Renal

Creatinine ≤ 2.0 mg/dL

Other

No active uncontrolled infection
- Infection under active treatment and controlled with antibiotics allowed
No other life-threatening illness
No mental deficit and/or psychiatric history that would preclude giving informed consent or study participation
No allergy to imidazoles (e.g., clotrimazole, ketoconazole, miconazole, or econazole)

PRIOR CONCURRENT THERAPY:

Biologic therapy

Prior thalidomide, interferon, or cytokines for MDS allowed
No concurrent immunotherapy

Chemotherapy

Prior hydroxyurea allowed
Prior azacytidine for MDS allowed
No prior etoposide
No other concurrent chemotherapy

Endocrine therapy

Not specified

Radiotherapy

No concurrent radiotherapy

Surgery

Not specified

Other

Other prior noncytotoxic therapy for MDS allowed
No prior tipifarnib
No concurrent antacids (magnesium- or aluminum-containing formulations) within 2 hours before or after study drug administration
No concurrent enzyme-inducing anticonvulsants (e.g., phenytoin, fosphenytoin, phenobarbital, primidone, carbamazepine, or oxcarbazepine)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00112853

Locations

United States, Florida
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
Tampa, Florida, United States, 33612-9497
United States, Georgia
Blood and Marrow Transplant Group of Georgia
Atlanta, Georgia, United States, 30342
United States, Maryland
Greenebaum Cancer Center at University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109-0942
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, New York
New York Weill Cornell Cancer Center at Cornell University
New York, New York, United States, 10021

Sponsors and Collaborators

Sidney Kimmel Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Judith E. Karp, MD

Sidney Kimmel Comprehensive Cancer Center

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:	CDR0000428305, JHOC-05020806, JHOC-J04110, NCI-6954
Study First Received:	June 2, 2005
Last Updated:	May 15, 2009
ClinicalTrials.gov Identifier:	NCT00112853 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

adult acute myeloblastic leukemia with maturation (M2)
adult acute myeloblastic leukemia without maturation (M1)
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute myelomonocytic leukemia (M4)
adult acute monoblastic leukemia (M5a)

adult acute monocytic leukemia (M5b)
adult pure erythroid leukemia (M6b)
adult erythroleukemia (M6a)
untreated adult acute myeloid leukemia
secondary acute myeloid leukemia
adult acute minimally differentiated myeloid leukemia (M0)
adult acute megakaryoblastic leukemia (M7)

Study placed in the following topic categories:

Leukemia, Monocytic, Acute
Acute Myelomonocytic Leukemia
Leukemia, Myeloid
Acute Monoblastic Leukemia
Leukemia, Myeloid, Acute
Etoposide phosphate
Leukemia, Myelomonocytic, Acute
Leukemia
Acute Myelocytic Leukemia

Acute Erythroblastic Leukemia
Leukemia, Erythroblastic, Acute
Acute Myeloid Leukemia, Adult
Neoplasm Metastasis
Congenital Abnormalities
Antineoplastic Agents, Phytogenic
Etoposide
Tipifarnib
Di Guglielmo's Syndrome

Additional relevant MeSH terms:

Leukemia
Neoplasms
Neoplasms by Histologic Type
Antineoplastic Agents
Therapeutic Uses
Leukemia, Myeloid

Leukemia, Myeloid, Acute
Antineoplastic Agents, Phytogenic
Etoposide phosphate
Etoposide
Pharmacologic Actions
Tipifarnib

ClinicalTrials.gov processed this record on August 30, 2009