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
Conditions
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.
Interventions
Given orally
Given orally
Sponsors
Study design
Eligibility
Inclusion 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
January 2008 and December 2009,
Pre-assignment details
5 patients signed consent, but were deemed screen failures and did not begin study treatment
Participants by arm
| Arm | Count |
|---|---|
| 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. | 63 |
| 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. | 21 |
| Total | 84 |
Baseline characteristics
| Characteristic | Arm II (Closed to Accrual as of November 2008) | Arm I | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 21 Participants | 63 Participants | 84 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 78 years STANDARD_DEVIATION 19 | 76 years STANDARD_DEVIATION 20 | 76 years STANDARD_DEVIATION 20 |
| Region of Enrollment United States | 21 participants | 63 participants | 84 participants |
| Sex: Female, Male Female | 7 Participants | 24 Participants | 31 Participants |
| Sex: Female, Male Male | 14 Participants | 39 Participants | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 18 / 63 | 6 / 21 |
| serious Total, serious adverse events | 5 / 63 | 8 / 21 |
Outcome results
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.
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I | Complete Response | 0 participants |
| Arm II (Closed to Accrual as of November 2008) | Complete Response | 0 participants |