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

Phase 2

Completed

• Conditions: Adult Acute Monoblastic Leukemia (M5a); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Secondary Acute Myeloid Leukemia; Adult Acute Myelomonocytic Leukemia (M4); Untreated Adult Acute Myeloid Leukemia; Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monocytic Leukemia (M5b)
• Interventions: Drug: tipifarnib; Drug: etoposide

• Registration Number: NCT00602771
• Lead Sponsor: National Cancer Institute (NCI)

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.

Study Timeline

• Study Start: 2008-01
• Study First Submitted: 2008-01-19
• Study First Submitted QC: 2008-01-24
• Study First Posted: 2008-01-28
• Primary Completion: 2011-10
• Study Completion: 2011-10
• Results First Submitted: 2013-01-08
• Results First Submitted QC: 2014-04-22
• Results First Posted: 2014-05-26
• Status Verified: 2014-06
• Last Update Submitted: 2014-10-01
• Last Update Posted: 2014-10-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 84

Inclusion Criteria

• 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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I	tipifarnib	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 (closed to accrual as of November 2008)	tipifarnib	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.
Arm I	etoposide	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 (closed to accrual as of November 2008)	etoposide	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.

Primary Outcome Measures

Name	Time	Method
Complete Response	6 months	Bone marrow showing less than 5% myeloblasts with normal maturation of all cell lines, an ANC of at least 1000/mcL and a platelet count of 100,000 mcL, absence of blast in peripheral blood, absence of identifiable leukemic cells in the bone marrow, clearance of disease-associated cytogenetic abnormalities, and clearance of any previously existing extramedullary disease. A CR must be confirmed 4 to 6 weeks after the initial documentation. If possible, at least one bone marrow biopsy should be performed to confirm the CR.

Trial Locations

Locations (5)

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Johns Hopkins University/Sidney Kimmel Cancer Center; 🇺🇸 Baltimore, Maryland, United States

Blood and Marrow Transplant Group of Georgia; 🇺🇸 Atlanta, Georgia, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Weill Medical College of Cornell University; 🇺🇸 New York, New York, United States