Tipifarnib and Etoposide in Treating Older Patients With Newly Diagnosed, Previously Untreated Acute Myeloid Leukemia

NCT ID: NCT00602771

Last Updated: 2014-10-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2011-10-31

Brief Summary

This randomized phase II trial is studying the side effects and how well giving tipifarnib together with etoposide works in treating older patients with newly diagnosed, previously untreated 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.

Detailed Description

OBJECTIVES:

I. To compare the efficacy and toxicity of two schedules of tipifarnib plus etoposide as induction therapy in older patients with newly diagnosed, previously untreated acute myeloid leukemia.

II. To study mechanisms of leukemia cell resistance to tipifarnib in combination with etoposide.

OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive 600 mg of oral tipifarnib twice daily on days 1-14 and 100 mg of oral etoposide once daily on days 1-3 and 8-10.

ARM II: Patients receive 400 mg of oral tipifarnib twice daily on days 1-14 and 200 mg of oral etoposide once daily on days 1-3 and 8-10. (closed to accrual as of November 2008)

Treatment in both arms repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 30 days and then every 90 days thereafter.

Conditions

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); 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 Del(5q); 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 Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

Patients receive 600 mg of oral tipifarnib twice daily on days 1-14 and 100 mg of oral etoposide once daily on days 1-3 and 8-10.

Group Type: EXPERIMENTAL

tipifarnib

Intervention Type: DRUG

Given orally

etoposide

Intervention Type: DRUG

Given orally

Arm II (closed to accrual as of November 2008)

Patients receive 400 mg of oral tipifarnib twice daily on days 1-14 and 200 mg of oral etoposide once daily on days 1-3 and 8-10.

Group Type: EXPERIMENTAL

tipifarnib

Intervention Type: DRUG

Given orally

etoposide

Intervention Type: DRUG

Given orally

Interventions

tipifarnib

Given orally

Intervention Type: DRUG

etoposide

Given orally

Intervention Type: DRUG

Other Intervention Names

R115777; Zarnestra; EPEG; VP-16; VP-16-213

Eligibility Criteria

Inclusion Criteria

• Must be considered ineligible for traditional antileukemia chemotherapy
• No hyperleukocytosis with ≥ 30,000 blasts/uL or rapidly rising blast count with projected doubling time of =< 2 days
• Patients may receive hydroxyurea to lower blast count to < 30,000 blasts/uL up to 24 hours before beginning tipifarnib and etoposide
• No active CNS leukemia
• No prior tipifarnib or etoposide
• No concurrent radiotherapy, immunotherapy, or other chemotherapy
• No concurrent enzyme-inducing anticonvulsants (e.g., phenytoin, fosphenytoin, phenobarbital, primidone, carbamazepine, or oxcarbazepine)
• Patients may be changed to non-enzyme-inducing anticonvulsants and stabilized before starting study treatment

• ECOG performance status 0-2
• Serum creatinine =< 2.0 mg/dL
• SGOT and SGPT =< 3 times upper limit of normal
• Bilirubin =< 2 mg/dL

Exclusion Criteria

• Active, uncontrolled infection
• Patients with infection under active treatment and controlled with antimicrobials are eligible
• Presence of other life-threatening illnesses
• Patients with mental deficits and/or psychiatric history that preclude them from giving informed consent or from following protocol
• Allergies to imidazoles (e.g., clotrimazole, ketoconazole, miconazole, or econazole)

• Minimum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Judith Karp

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University/Sidney Kimmel Cancer Center

Locations

Blood and Marrow Transplant Group of Georgia

Atlanta, Georgia, United States

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

University of Michigan

Ann Arbor, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

Weill Medical College of Cornell University

New York, New York, United States

Countries

United States

References

Ding H, McDonald JS, Yun S, Schneider PA, Peterson KL, Flatten KS, Loegering DA, Oberg AL, Riska SM, Huang S, Sinicrope FA, Adjei AA, Karp JE, Meng XW, Kaufmann SH. Farnesyltransferase inhibitor tipifarnib inhibits Rheb prenylation and stabilizes Bax in acute myelogenous leukemia cells. Haematologica. 2014 Jan;99(1):60-9. doi: 10.3324/haematol.2013.087734. Epub 2013 Aug 30.

Reference Type: DERIVED

PMID: 23996484 (View on PubMed)

Karp JE, Vener TI, Raponi M, Ritchie EK, Smith BD, Gore SD, Morris LE, Feldman EJ, Greer JM, Malek S, Carraway HE, Ironside V, Galkin S, Levis MJ, McDevitt MA, Roboz GR, Gocke CD, Derecho C, Palma J, Wang Y, Kaufmann SH, Wright JJ, Garret-Mayer E. Multi-institutional phase 2 clinical and pharmacogenomic trial of tipifarnib plus etoposide for elderly adults with newly diagnosed acute myelogenous leukemia. Blood. 2012 Jan 5;119(1):55-63. doi: 10.1182/blood-2011-08-370825. Epub 2011 Oct 14.

Reference Type: DERIVED

PMID: 22001391 (View on PubMed)

Other Identifiers

NCI-2009-00278

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000584212

Identifier Type: -

Identifier Source: secondary_id

J07109

Identifier Type: OTHER

Identifier Source: secondary_id

8077

Identifier Type: OTHER

Identifier Source: secondary_id

N01CM62204

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA006973

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA070095

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00278

Identifier Type: -

Identifier Source: org_study_id