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 phase II trial studies the side effects and how well omacetaxine mepesuccinate, cytarabine, and decitabine work in treating older patients with newly diagnosed acute myeloid leukemia. Omacetaxine mepesuccinate, cytarabine, and decitabine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVES: I. To study the complete response rate following OAG (omacetaxine mepesuccinate, cytarabine) in newly diagnosed acute myeloid leukemia patients unfit for intensive induction therapy. II. To assess the toxicity of OAG using the Cancer Therapy Evaluation Program (CTEP) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE version 4.0). SECONDARY OBJECTIVES: I. To study the disease-free and overall survival of OAG and decitabine in newly diagnosed acute myeloid leukemia patients unfit for intensive induction therapy. OUTLINE: INDUCTION CHEMOTHERAPY: Patients receive cytarabine subcutaneously (SC) twice daily (BID) and omacetaxine mepesuccinate SC BID on days 1-14. Treatment for induction therapy repeats every 28 days for up to 4 courses or until patients achieve complete response (CR) in the absence of disease progression or unacceptable toxicity. CONSOLIDATION THERAPY: Patients alternate courses between decitabine and OAG. Patients receive decitabine intravenously (IV) on days 1-5. Patients alternate with OAG courses, comprising cytarabine SC BID on days 1-7 and omacetaxine mepesuccinate SC BID on days 1-7. Treatment repeats every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.
Interventions
Given SC
Given SC
Given IV
Correlative studies
Sponsors
Study design
Eligibility
Inclusion criteria
* Patients who are not eligible for standard induction chemotherapy (or any standard therapy known to be life prolonging) because of poor performance status, significant tissue comorbidities, or unfavorable risk of disease * Have an unequivocal histologic diagnosis of acute myeloid leukemia (AML) (including secondary AML) * No prior therapy for AML except hydroxyurea to control counts * Must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation * Subject or legal representative must understand the investigational nature of this study and sign an independent ethics committee/institutional review board approved written informed consent form prior to receiving any study related procedure
Exclusion criteria
* Subjects with the diagnosis of acute promyelocytic leukemia (t\[15;17\]) * Unwilling or unable to follow protocol requirements * Any condition which in the investigator's opinion deems the subject an unsuitable candidate to receive study drug * Patients with sickle cell disease and sickle cell crisis * Received an investigational agent for another disease within 30 days prior to enrollment * The patient has an uncontrolled and active infection that would preclude study conduct and assessment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of the Evaluable Population of Interest Who Experience a Complete Response in the Poor and Good Prognosis Groups | Up to 4 years | Defined as recovery of morphologically normal bone marrow (\< 5% blasts) and blood counts (absolute neutrophil count \>= 1x10\^9/L, platelet counts \>= 100x10\^9/LO) and rare circulating leukemic blasts or evidence of extramedullary disease. Analyzed using exact binomial probabilities in a two-stage design. The number of responses will be tabulated. |
| Frequency of Adverse Events, Graded According to NCI CTCAE v4.0 | Up to 30 days after last dose of study drugs | Maximum grade per participant of any AE. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Cytarabine, Omacetaxine Mepesuccinate, Decitabine) INDUCTION CHEMOTHERAPY: Patients receive cytarabine SC BID and omacetaxine mepesuccinate SC BID on days 1-14. Treatment for induction therapy repeats every 28 days for up to 4 courses or until patients achieve CR in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION THERAPY: Patients alternate courses between decitabine and OAG. Patients receive decitabine IV on days 1-5. Patients alternate with OAG courses, comprising cytarabine SC BID on days 1-7 and omacetaxine mepesuccinate SC BID on days 1-7. Treatment repeats every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
cytarabine: Given SC
omacetaxine mepesuccinate: Given SC
decitabine: Given IV
laboratory biomarker analysis: Correlative studies | 2 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 1 |
Baseline characteristics
| Characteristic | Treatment (Cytarabine, Omacetaxine Mepesuccinate, Decitabine) |
|---|---|
| Age, Continuous | 75 years STANDARD_DEVIATION 1.8 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 2 |
| serious Total, serious adverse events | 2 / 2 |
Outcome results
Frequency of Adverse Events, Graded According to NCI CTCAE v4.0
Maximum grade per participant of any AE.
Time frame: Up to 30 days after last dose of study drugs
Population: All treated and eligible patients.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Cytarabine, Omacetaxine Mepesuccinate, Decitabine) | Frequency of Adverse Events, Graded According to NCI CTCAE v4.0 | Grade 1 | 0 participants |
| Treatment (Cytarabine, Omacetaxine Mepesuccinate, Decitabine) | Frequency of Adverse Events, Graded According to NCI CTCAE v4.0 | Grade 2 | 0 participants |
| Treatment (Cytarabine, Omacetaxine Mepesuccinate, Decitabine) | Frequency of Adverse Events, Graded According to NCI CTCAE v4.0 | Grade 3 | 0 participants |
| Treatment (Cytarabine, Omacetaxine Mepesuccinate, Decitabine) | Frequency of Adverse Events, Graded According to NCI CTCAE v4.0 | Grade 4 | 2 participants |
Proportion of the Evaluable Population of Interest Who Experience a Complete Response in the Poor and Good Prognosis Groups
Defined as recovery of morphologically normal bone marrow (\< 5% blasts) and blood counts (absolute neutrophil count \>= 1x10\^9/L, platelet counts \>= 100x10\^9/LO) and rare circulating leukemic blasts or evidence of extramedullary disease. Analyzed using exact binomial probabilities in a two-stage design. The number of responses will be tabulated.
Time frame: Up to 4 years
Population: Due to the study's early termination and low accrual, data were not collected for this assessment.