Myelodysplastic Syndrome
Conditions
Keywords
Myelodysplastic Syndrome, Decitabine, Dacogen, MGI PHARMA, Inc.
Brief summary
The purpose of this study is to determine the effectiveness and safety of two different dose schedules of DACOGEN® (decitabine) for Injection in patients with Myelodysplastic Syndromes (MDS).
Detailed description
This is a randomized open-label Phase 2 efficacy and safety study of two (2) subcutaneous (SQ) dosing schedules of decitabine in subjects with Low or Intermediate 1 Risk MDS. This study will be conducted in up to 6 study centers in the United States. The primary efficacy outcome is the overall improvement rate. These two doses will be administered subcutaneously. The probability that one schedule is superior to the other will be estimated, and the level of toxicity for each schedule will also be evaluated.
Interventions
DRUGdecitabine
Schedule A: decitabine will be administered subcutaneously (SQ) daily for 3 consecutive days (Days 1 to 3) every 28 days. The dose will be 20 mg/m\^2/day. One course will be considered 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
Each patient must meet the following criteria to be enrolled in this study: 1. Male or female patients age 18 years and older. 2. Patients must sign an institutional review board (IRB)-approved informed consent form, and understand the investigational nature of this study and its potential hazards prior to initiation of any study-specific procedures or treatment. 3. Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. 4. Adequate renal and hepatic function (creatinine \< 2 times upper limit of normal, total bilirubin of \< 2 times upper limit of normal, and AST and ALT ≤ 2 times upper limit of normal) unless proven to be related to disease infiltration. 5. Female patients need a negative serum or urine pregnancy test within 7 days prior to study drug administration (applies only if patient is of childbearing potential. Non-childbearing is defined as ≥ 1 year postmenopausal or surgically sterilized). 6. Women of childbearing potential and men must use contraception. Men and women must continue birth control for the duration of the study. 7. Patients with Low or Intermediate-1 Risk MDS by the International Prognostic Scoring System (IPSS) classification.
Exclusion criteria
Patients who meet any of the following criteria will be excluded from the study: 1. Women who are pregnant or nursing. 2. Those who have received prior therapy with decitabine. 3. Prior therapy with azacitidine (Vidaza®). 4. Those who received growth factor support or lenalidomide in the 30 days prior to the first dose of decitabine. 5. Those who have received an investigational agent 30 days prior to the first dose of decitabine. 6. Patients with active, uncontrolled, systemic infection considered opportunistic, life threatening or clinically significant; or any severe, concurrent disease, which, in the judgment of the Investigator and after discussion with the Sponsor and Primary Investigator, would make the patient inappropriate for study entry.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Overall Improvement Rate | Up to one year | Defined as proportion of patients having complete remission (CR), partial remission (PR), marrow complete remission (mCR), or hematologic improvement. Based on Modified International Working Group Response Criteria for Altering Natural History of Myelodysplastic Syndromes. Complete Remission: 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 109/L; Neutrophils ≥ 1.0 X 109/Lb; Blasts 0%. Partial Remission: All CR criteria if abnormal before treatment except: Bone marrow blasts decreased by ≥ 50% over pretreatment but still \> 5%. Marrow Complete Remission: 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. HI Improvement: shown in increases in hemoglobin, platelet and neutrophil response. |
Countries
United States
Participant flow
Recruitment details
This study was recruited at 5 centers in U.S. during the period of Jun 2008 to Aug 2011.
Participants by arm
| Arm | Count |
|---|---|
| Schedule A: SQ 3 Consecutive Days Decitabine : Schedule A: decitabine will be administered subcutaneously (SQ) daily for 3 consecutive days (Days 1 to 3) every 28 days. The dose will be 20 mg/m\^2/day. One course will be considered 28 days. | 43 |
| Schedule B: SQ Once Every 7 Days Decitabine : Schedule B: decitabine will be administered SQ every 7 days for 21 days (Days 1, 8, and 15) followed by 7 days without an administration of decitabine. The dose will be 20 mg/m\^2/day. One course will be considered 28 days. | 22 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 3 |
| Overall Study | Allogeneic Bone Marrow Transplantation | 2 | 1 |
| Overall Study | Emergence of Clinically Significant Lab | 1 | 2 |
| Overall Study | Physician Decision | 9 | 6 |
| Overall Study | Progressive Disease | 7 | 5 |
| Overall Study | Withdrawal by Subject | 10 | 2 |
Baseline characteristics
| Characteristic | Schedule B: SQ Once Every 7 Days | Total | Schedule A: SQ 3 Consecutive Days |
|---|---|---|---|
| Age Continuous | 70.5 years STANDARD_DEVIATION 9.86 | 68.2 years STANDARD_DEVIATION 13.07 | 66.9 years STANDARD_DEVIATION 14.39 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 62 Participants | 42 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 5 Participants | 5 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 | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 20 Participants | 55 Participants | 35 Participants |
| Sex: Female, Male Female | 2 Participants | 20 Participants | 18 Participants |
| Sex: Female, Male Male | 20 Participants | 45 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 43 / 43 | 22 / 22 |
| serious Total, serious adverse events | 18 / 43 | 10 / 22 |
Outcome results
Primary
The Overall Improvement Rate
Defined as proportion of patients having complete remission (CR), partial remission (PR), marrow complete remission (mCR), or hematologic improvement. Based on Modified International Working Group Response Criteria for Altering Natural History of Myelodysplastic Syndromes. Complete Remission: 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 109/L; Neutrophils ≥ 1.0 X 109/Lb; Blasts 0%. Partial Remission: All CR criteria if abnormal before treatment except: Bone marrow blasts decreased by ≥ 50% over pretreatment but still \> 5%. Marrow Complete Remission: 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. HI Improvement: shown in increases in hemoglobin, platelet and neutrophil response.
Time frame: Up to one year
Population: Modified Intent to Treat (mITT) Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Schedule A: SQ 3 Consecutive Days | The Overall Improvement Rate | Complete Response | 16.3 Percentage of Participants |
| Schedule A: SQ 3 Consecutive Days | The Overall Improvement Rate | Partial Response | 0 Percentage of Participants |
| Schedule A: SQ 3 Consecutive Days | The Overall Improvement Rate | Marrow Complete Response | 0 Percentage of Participants |
| Schedule A: SQ 3 Consecutive Days | The Overall Improvement Rate | Hematologic Improvement | 7.0 Percentage of Participants |
| Schedule A: SQ 3 Consecutive Days | The Overall Improvement Rate | Overall Improvement Rate | 23.3 Percentage of Participants |
| Schedule B: SQ Once Every 7 Days | The Overall Improvement Rate | Hematologic Improvement | 13.6 Percentage of Participants |
| Schedule B: SQ Once Every 7 Days | The Overall Improvement Rate | Overall Improvement Rate | 22.7 Percentage of Participants |
| Schedule B: SQ Once Every 7 Days | The Overall Improvement Rate | Complete Response | 0 Percentage of Participants |
| Schedule B: SQ Once Every 7 Days | The Overall Improvement Rate | Marrow Complete Response | 4.5 Percentage of Participants |
| Schedule B: SQ Once Every 7 Days | The Overall Improvement Rate | Partial Response | 4.5 Percentage of Participants |