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

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Clinical Trial

Official title:

A Randomized Phase II Trial of Tipifarnib (R115777, ZARNESTRA, NSC #702818) in Combination With Oral Etoposide (VP-16) in Elderly Adults With Newly Diagnosed, Previously Untreated Acute Myelogenous Leukemia (AML)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00602771
• Other study ID #: NCI-2009-00278
• Secondary ID: NCI-2009-00278CD
• Status: Completed
• Phase: Phase 2
• First received: January 19, 2008
• Last updated: October 1, 2014
• Start date: January 2008
• Est. completion date: October 2011

Study information

• Verified date: June 2014
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 70 Years and older

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• 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)
• Leukemia
• Leukemia, Erythroblastic, Acute
• Leukemia, Megakaryoblastic, Acute
• Leukemia, Monocytic, Acute
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Leukemia, Myelomonocytic, Acute
• Leukemia, Myelomonocytic, Chronic
• Myelodysplastic Syndromes
• Preleukemia
• Secondary Acute Myeloid Leukemia
• Untreated Adult Acute Myeloid Leukemia

Intervention

Drug:
• tipifarnib
Given orally
• etoposide
Given orally

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Blood and Marrow Transplant Group of Georgia	Atlanta	Georgia
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	Weill Medical College of Cornell University	New York	New York
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Response	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.	6 months	No