Myelodysplastic Syndromes
Conditions
Keywords
MDS, Myelodysplastic Syndromes
Brief summary
The purpose of this study is to compare the response of patients with Intermediate or High Risk myelodysplastic syndromes (MDS) following treatment with decitabine or azacitidine.
Interventions
DRUGdecitabine
decitabine 20 mg/m\^2 /day intravenous (IV) infusion for 5 days every 28 days
DRUGazacitidine
azacitidine 75 mg/m\^2 /day subcutaneous (SC) injection for 7 days every 28 days
Sponsors
Eisai Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subjects who meet all of the following criteria may be included in the study: 1. Must have a diagnosis of primary myelodysplastic syndromes (MDS) of Intermediate-1 transfusion dependent, Intermediate-2, or High-risk \[defined by International Prognostic Scoring System (IPSS) score of ≥0.5\] and recognized French-American-British (FAB) classifications 2. Male or female, 18 years of age or older with signed informed consent 3. Adequate renal function 4. Demonstrated normal liver function 5. Female subjects of childbearing age must have negative pregnancy test within 1 week of study entry and agree to use adequate contraception for the duration of the trial and for a minimum of six months after last dose of decitabine or azacitidine received. 6. Male subjects must agree to use adequate contraception for the duration of the trial and for a minimum of six months after last dose of decitabine or azacitidine received.
Exclusion criteria
Subjects who meet any of the following criteria will be excluded from participation in the study: 1. Current use of radiotherapy for extramedullary disease for 2 weeks prior to entering study (permitted if \> 2 weeks from study entry and if recovered from toxic effects of therapy) 2. Systemic fungal, bacterial, or viral infection which is not controlled (i.e., ongoing signs or symptoms of infection and without improvement despite appropriate treatment) 3. Pregnancy or current lactation 4. Significant concurrent disease, illness, or psychiatric disorder 5. Treatment with an investigational agent 30 days prior to the first dose of decitabine or azacitidine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR), Defined as Proportion of Patients Having Complete Response (CR) and Marrow Complete Response (mCR) After Completion of 3 Cycles of Study Drug. | 13 Weeks | Based on Modified International Working Group Response Criteria for Altering Natural History of Myelodysplastic Syndromes. Complete Response: Bone marrow: ≤ 5% myeloblasts with normal maturation of all cell lines. Persistent dysplasia will be noted. Peripheral blood Hgb ≥ 11 g/dL; Platelets ≥ 100 X 10\^9/L; Neutrophils ≥ 1.0 X 10\^9/Lb; Blasts 0%. Marrow Complete Response: Bone marrow: ≤ 5% myeloblasts and decrease by ≥ 50% over pretreatment. Peripheral blood: if hematological improvement responses, they will be noted in addition to marrow CR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR), Defined as Proportion of Patients Having Complete Response (CR) and Marrow Complete Response (mCR) After Completion of 6 Cycles of Study Drug. | 36 Weeks | Based on Modified International Working Group Response Criteria for Altering Natural History of Myelodysplastic Syndromes. Complete Response: Bone marrow: ≤ 5% myeloblasts with normal maturation of all cell lines. Persistent dysplasia will be noted. Peripheral blood Hgb ≥ 11 g/dL; Platelets ≥ 100 X 10\^9/L; Neutrophils ≥ 1.0 X 10\^9/Lb; Blasts 0%. Marrow Complete Response: Bone marrow: ≤ 5% myeloblasts and decrease by ≥ 50% over pretreatment. Peripheral blood: if hematological improvement responses, they will be noted in addition to marrow CR. |
Countries
United States
Participant flow
Recruitment details
This study was recruited at 20 centers in U.S. during the period of Feb 2010 to Jan 2011.
Participants by arm
| Arm | Count |
|---|---|
| Decitabine 20 mg/m^2 decitabine : decitabine 20 mg/m\^2 /day intravenous (IV) infusion for 5 days every 28 days | 13 |
| Azacitidine 75 mg/m^2 azacitidine : azacitidine 75 mg/m\^2 /day subcutaneous (SC) injection for 7 days every 28 days | 13 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 2 |
| Overall Study | Other | 2 | 2 |
| Overall Study | Progressive Disease | 0 | 2 |
| Overall Study | Terminated by Sponsor | 5 | 5 |
Baseline characteristics
| Characteristic | Azacitidine 75 mg/m^2 | Total | Decitabine 20 mg/m^2 |
|---|---|---|---|
| Age, Continuous | 70.8 years STANDARD_DEVIATION 9.13 | 72.3 years STANDARD_DEVIATION 10.35 | 73.8 years STANDARD_DEVIATION 11.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 24 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 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 | 12 Participants | 25 Participants | 13 Participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 2 Participants |
| Sex: Female, Male Male | 10 Participants | 21 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 13 | 13 / 13 |
| serious Total, serious adverse events | 7 / 13 | 7 / 13 |
Outcome results
Primary
Overall Response Rate (ORR), Defined as Proportion of Patients Having Complete Response (CR) and Marrow Complete Response (mCR) After Completion of 3 Cycles of Study Drug.
Based on Modified International Working Group Response Criteria for Altering Natural History of Myelodysplastic Syndromes. Complete Response: Bone marrow: ≤ 5% myeloblasts with normal maturation of all cell lines. Persistent dysplasia will be noted. Peripheral blood Hgb ≥ 11 g/dL; Platelets ≥ 100 X 10\^9/L; Neutrophils ≥ 1.0 X 10\^9/Lb; Blasts 0%. Marrow Complete Response: Bone marrow: ≤ 5% myeloblasts and decrease by ≥ 50% over pretreatment. Peripheral blood: if hematological improvement responses, they will be noted in addition to marrow CR.
Time frame: 13 Weeks
Population: Intent to Treat Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Decitabine 20 mg/m^2 | Overall Response Rate (ORR), Defined as Proportion of Patients Having Complete Response (CR) and Marrow Complete Response (mCR) After Completion of 3 Cycles of Study Drug. | Complete Response | 0 Percentage of Participants |
| Decitabine 20 mg/m^2 | Overall Response Rate (ORR), Defined as Proportion of Patients Having Complete Response (CR) and Marrow Complete Response (mCR) After Completion of 3 Cycles of Study Drug. | Partial Response | 0 Percentage of Participants |
| Decitabine 20 mg/m^2 | Overall Response Rate (ORR), Defined as Proportion of Patients Having Complete Response (CR) and Marrow Complete Response (mCR) After Completion of 3 Cycles of Study Drug. | Marrow Complete Response | 0 Percentage of Participants |
| Decitabine 20 mg/m^2 | Overall Response Rate (ORR), Defined as Proportion of Patients Having Complete Response (CR) and Marrow Complete Response (mCR) After Completion of 3 Cycles of Study Drug. | Stable Disease | 45.5 Percentage of Participants |
| Decitabine 20 mg/m^2 | Overall Response Rate (ORR), Defined as Proportion of Patients Having Complete Response (CR) and Marrow Complete Response (mCR) After Completion of 3 Cycles of Study Drug. | Overall Response Rate | 0 Percentage of Participants |
| Azacitidine 75 mg/m^2 | Overall Response Rate (ORR), Defined as Proportion of Patients Having Complete Response (CR) and Marrow Complete Response (mCR) After Completion of 3 Cycles of Study Drug. | Stable Disease | 25.0 Percentage of Participants |
| Azacitidine 75 mg/m^2 | Overall Response Rate (ORR), Defined as Proportion of Patients Having Complete Response (CR) and Marrow Complete Response (mCR) After Completion of 3 Cycles of Study Drug. | Overall Response Rate | 0 Percentage of Participants |
| Azacitidine 75 mg/m^2 | Overall Response Rate (ORR), Defined as Proportion of Patients Having Complete Response (CR) and Marrow Complete Response (mCR) After Completion of 3 Cycles of Study Drug. | Complete Response | 0 Percentage of Participants |
| Azacitidine 75 mg/m^2 | Overall Response Rate (ORR), Defined as Proportion of Patients Having Complete Response (CR) and Marrow Complete Response (mCR) After Completion of 3 Cycles of Study Drug. | Marrow Complete Response | 0 Percentage of Participants |
| Azacitidine 75 mg/m^2 | Overall Response Rate (ORR), Defined as Proportion of Patients Having Complete Response (CR) and Marrow Complete Response (mCR) After Completion of 3 Cycles of Study Drug. | Partial Response | 0 Percentage of Participants |
Secondary
Overall Response Rate (ORR), Defined as Proportion of Patients Having Complete Response (CR) and Marrow Complete Response (mCR) After Completion of 6 Cycles of Study Drug.
Based on Modified International Working Group Response Criteria for Altering Natural History of Myelodysplastic Syndromes. Complete Response: Bone marrow: ≤ 5% myeloblasts with normal maturation of all cell lines. Persistent dysplasia will be noted. Peripheral blood Hgb ≥ 11 g/dL; Platelets ≥ 100 X 10\^9/L; Neutrophils ≥ 1.0 X 10\^9/Lb; Blasts 0%. Marrow Complete Response: Bone marrow: ≤ 5% myeloblasts and decrease by ≥ 50% over pretreatment. Peripheral blood: if hematological improvement responses, they will be noted in addition to marrow CR.
Time frame: 36 Weeks
Population: Intent to Treat Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Decitabine 20 mg/m^2 | Overall Response Rate (ORR), Defined as Proportion of Patients Having Complete Response (CR) and Marrow Complete Response (mCR) After Completion of 6 Cycles of Study Drug. | Complete Response | 9.1 Percentage of Participants |
| Decitabine 20 mg/m^2 | Overall Response Rate (ORR), Defined as Proportion of Patients Having Complete Response (CR) and Marrow Complete Response (mCR) After Completion of 6 Cycles of Study Drug. | Overall Response Rate | 9.1 Percentage of Participants |
| Decitabine 20 mg/m^2 | Overall Response Rate (ORR), Defined as Proportion of Patients Having Complete Response (CR) and Marrow Complete Response (mCR) After Completion of 6 Cycles of Study Drug. | Marrow Complete Response | 0 Percentage of Participants |
| Decitabine 20 mg/m^2 | Overall Response Rate (ORR), Defined as Proportion of Patients Having Complete Response (CR) and Marrow Complete Response (mCR) After Completion of 6 Cycles of Study Drug. | Partial Response | 9.1 Percentage of Participants |
| Decitabine 20 mg/m^2 | Overall Response Rate (ORR), Defined as Proportion of Patients Having Complete Response (CR) and Marrow Complete Response (mCR) After Completion of 6 Cycles of Study Drug. | Stable Disease | 36.4 Percentage of Participants |
| Azacitidine 75 mg/m^2 | Overall Response Rate (ORR), Defined as Proportion of Patients Having Complete Response (CR) and Marrow Complete Response (mCR) After Completion of 6 Cycles of Study Drug. | Stable Disease | 16.7 Percentage of Participants |
| Azacitidine 75 mg/m^2 | Overall Response Rate (ORR), Defined as Proportion of Patients Having Complete Response (CR) and Marrow Complete Response (mCR) After Completion of 6 Cycles of Study Drug. | Partial Response | 0 Percentage of Participants |
| Azacitidine 75 mg/m^2 | Overall Response Rate (ORR), Defined as Proportion of Patients Having Complete Response (CR) and Marrow Complete Response (mCR) After Completion of 6 Cycles of Study Drug. | Marrow Complete Response | 0 Percentage of Participants |
| Azacitidine 75 mg/m^2 | Overall Response Rate (ORR), Defined as Proportion of Patients Having Complete Response (CR) and Marrow Complete Response (mCR) After Completion of 6 Cycles of Study Drug. | Overall Response Rate | 8.3 Percentage of Participants |
| Azacitidine 75 mg/m^2 | Overall Response Rate (ORR), Defined as Proportion of Patients Having Complete Response (CR) and Marrow Complete Response (mCR) After Completion of 6 Cycles of Study Drug. | Complete Response | 8.3 Percentage of Participants |