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

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2

Conditions: Adult Acute Megakaryoblastic Leukemia (M7); Adult Erythroleukemia (M6a); Untreated Adult Acute Myeloid Leukemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Pure Erythroid Leukemia (M6b); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Myeloblastic Leukemia With Maturation (M2); Secondary Acute Myeloid Leukemia; Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monocytic Leukemia (M5b); Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia With Del(5q)

Treatments: Drug: etoposide; Drug: tipifarnib

Study type: Interventional

Funder types: NIH

Identifiers

NCT00602771

U01CA070095 (U.S. NIH Grant/Contract)

8077 (Other Identifier)

P30CA006973 (U.S. NIH Grant/Contract)

NCI-2009-00278 (Registry Identifier)

J07109 (Other Identifier)

N01CM62204 (U.S. NIH Grant/Contract)

CDR0000584212

Details and patient eligibility

About

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.

Full 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.

Enrollment: 84 patients

Sex: All

Ages: 70+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Criteria:

• Pathologically confirmed newly diagnosed acute myeloid leukemia (AML)
• Subtypes M0, M1, M2, M4-7 disease
• No newly diagnosed acute promyelocytic leukemia (M3)
• Any of the following diseases:
• De novo disease
• Secondary AML
• Myelodysplasia (MDS)-related AML (MDS/AML)
• Treatment-related AML
• Previously untreated disease
• Patients who have received prior hydroxyurea alone or non-cytotoxic therapies for MDS (e.g., thalidomide, interferon, cytokines, 5-azacytidine, or revlimid) will be eligible for this study
• 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

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

84 participants in 2 patient groups

Arm I

Experimental group

Description:

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.

Treatment:

Drug: tipifarnib

Drug: etoposide

Arm II (closed to accrual as of November 2008)

Experimental group

Description:

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.

Treatment:

Drug: tipifarnib

Drug: etoposide