Acute Myeloid Leukemia
Conditions
Keywords
Acute Myeloid Leukemia, Dacogen, Decitabine, Poor or intermediate-risk cytogenetics
Brief summary
The purpose of this study is to compare the results in older patients who have newly diagnosed or secondary acute myeloid leukemia (AML) and who are to either receive decitabine or patient's choice with the physician's advice of either cytarabine or supportive care medication.
Interventions
DRUGCytarabine or Supportive Care
Patient's choice with physician's advice of either supportive care (IV fluids, nutrition, and antibiotics as needed) or cytarabine 20 mg/m\^2 subcutaneously once daily for the first 10 consecutive days of each 28 day cycle, until progression or unacceptable toxicity develops. (These represent one intervention.)
DRUGDacogen (decitabine) only
20mg/m\^2, 1 hour intravenous (IV) for 5 consecutive days of each 28 day cycle. Cycles continue until disease progression or unacceptable toxicity develops.
Sponsors
Eisai Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Must have diagnosed acute myeloid leukemia. 2. Must have a life expectancy of at least 12 weeks. 3. Must sign informed consent.
Exclusion criteria
1. Must not have acute promyelocytic leukemia (M3 classification) 2. Must not have any other active systemic malignancies. 3. Must not have inaspirable bone marrow. 4. Must not have received previous chemotherapy (except hydroxyurea) for any myeloid disorder. 5. Must not have chronic respiratory disease that requires continuous oxygen use. 6. Must not have received any experimental drug within 4 weeks before randomization. 7. Must not be a candidate for a bone marrow or stem cell transplant within 12 weeks after randomization. 8. Must not have known HIV.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival in Patients 65 Years or Older Who Have Newly Diagnosed de Novo or Secondary AML. | The interval from date of randomization to the date of death from any cause or the last date the subject was known to be alive or 5 years whichever occurs first. | The interval from date of randomization to the date of death from any cause or the last date the subject was known to be alive or 5 years whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Complete Remission (CR) Plus Complete Remission With Incomplete Platelet Recovery (CRp) | Post randomization when at least one post-baseline bone marrow assessment or peripheral blood count data available (up to 29.5 months) | Morphologic CR plus CRp rate where Morphologic leukemia-free state defined as less that (\<) 5 percent (%) blasts in an aspirate sample with marrow spicules and a count of greater than or equal to (\>=) 200 nucleated cells (there should have been no blasts with Auer rods or persistence of extramedullary disease) plus absolute neutrophil count (ANC) greater than (\>)1,000 per microliter (/mcL), platelet count of \>=100,000/mcL, and the participant must have been independent of transfusions for at least 1 week before each assessment. There was no duration requirement for confirmation of this designation and Morphologic CR without the requirement of platelet count \>=100,000/mcL. |
Countries
Australia, Canada, Croatia, Czechia, France, Hungary, Mexico, Poland, Romania, Russia, Serbia, Spain, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
This study was recruited at 65 centers in 12 countries during the period of 2006 to 2009.
Pre-assignment details
Prior to randomization, subjects indicated their preference for treatment, with physician's advice, or either cytarabine or supportive care in the event they were randomized to Arm A.
Participants by arm
| Arm | Count |
|---|---|
| Cytarabine or Supportive Care Subject's choice of treatment with physician's advice of either supportive care (IV fluids, nutrition, and antibiotics as needed) or cytarabine 20 mg/m\^2 given subcutaneously once daily for 10 consecutive days, repeated every 4 weeks. (These represent one intervention.) | 243 |
| Dacogen (Decitabine) Only 20 mg/m\^2 Dacogen (decitabine) given as 1-hour infusion once daily for 5 consecutive days every 4 weeks. | 242 |
| Total | 485 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 26 | 19 |
| Overall Study | Death | 43 | 62 |
| Overall Study | Other | 10 | 7 |
| Overall Study | Physician Decision | 15 | 9 |
| Overall Study | Progression | 116 | 96 |
| Overall Study | Protocol Violation | 3 | 1 |
| Overall Study | Withdrawal by Subject | 15 | 17 |
Baseline characteristics
| Characteristic | Total | Cytarabine or Supportive Care | Dacogen (Decitabine) Only |
|---|---|---|---|
| Age, Continuous | 73.34 years STANDARD_DEVIATION 5.46 | 73.53 years STANDARD_DEVIATION 5.67 | 73.14 years STANDARD_DEVIATION 5.24 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 60 Participants | 27 Participants | 33 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 422 Participants | 213 Participants | 209 Participants |
| Sex: Female, Male Female | 197 Participants | 92 Participants | 105 Participants |
| Sex: Female, Male Male | 288 Participants | 151 Participants | 137 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 231 / 237 | 237 / 238 |
| serious Total, serious adverse events | 162 / 237 | 190 / 238 |
Outcome results
Primary
Overall Survival in Patients 65 Years or Older Who Have Newly Diagnosed de Novo or Secondary AML.
The interval from date of randomization to the date of death from any cause or the last date the subject was known to be alive or 5 years whichever occurs first.
Time frame: The interval from date of randomization to the date of death from any cause or the last date the subject was known to be alive or 5 years whichever occurs first.
Population: The primary population for all efficacy analyses was the Intent-to-treat (ITT) population defined as all subjects randomly allocated to a treatment arm.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cytarabine or Supportive Care | Overall Survival in Patients 65 Years or Older Who Have Newly Diagnosed de Novo or Secondary AML. | 5.0 months |
| Dacogen (Decitabine) Only | Overall Survival in Patients 65 Years or Older Who Have Newly Diagnosed de Novo or Secondary AML. | 7.7 months |
Comparison: The primary treatment comparison was based on two sided long-rank test stratified by age, cytogenetic risk, ECOG performance statusp-value: 0.1079Kaplan-Meier
Secondary
Percentage of Participants With Complete Remission (CR) Plus Complete Remission With Incomplete Platelet Recovery (CRp)
Morphologic CR plus CRp rate where Morphologic leukemia-free state defined as less that (\<) 5 percent (%) blasts in an aspirate sample with marrow spicules and a count of greater than or equal to (\>=) 200 nucleated cells (there should have been no blasts with Auer rods or persistence of extramedullary disease) plus absolute neutrophil count (ANC) greater than (\>)1,000 per microliter (/mcL), platelet count of \>=100,000/mcL, and the participant must have been independent of transfusions for at least 1 week before each assessment. There was no duration requirement for confirmation of this designation and Morphologic CR without the requirement of platelet count \>=100,000/mcL.
Time frame: Post randomization when at least one post-baseline bone marrow assessment or peripheral blood count data available (up to 29.5 months)
Population: The primary population for all efficacy analyses was the ITT population defined as all participant randomly allocated to a treatment arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cytarabine or Supportive Care | Percentage of Participants With Complete Remission (CR) Plus Complete Remission With Incomplete Platelet Recovery (CRp) | 7.8 percentage of participants |
| Dacogen (Decitabine) Only | Percentage of Participants With Complete Remission (CR) Plus Complete Remission With Incomplete Platelet Recovery (CRp) | 17.8 percentage of participants |
p-value: 0.001195% CI: [1.4, 4.78]Fisher Exact