A Study of Decitabine Given Subcutaneously to Adults With Low or Intermediate-1 Risk Myelodysplastic Syndromes (MDS)

Study Overview
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Brief Summary
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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
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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.

Official Title
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Randomized Open-label Phase 2 Study of Low Dose Dacogen® for Injection (Decitabine) in Patients With Low or Intermediate 1 Risk Myelodysplastic Syndromes

Conditions
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Myelodysplastic Syndrome

Intervention / Treatment
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* Drug: decitabine
* Drug: decitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Each patient must meet the following criteria to be enrolled in this study: Male or female patients age 18 years and older. 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. Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. 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. 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). Women of childbearing potential and men must use contraception. Men and women must continue birth control for the duration of the study. 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: Women who are pregnant or nursing. Those who have received prior therapy with decitabine. Prior therapy with azacitidine (Vidaza®). Those who received growth factor support or lenalidomide in the 30 days prior to the first dose of decitabine. Those who have received an investigational agent 30 days prior to the first dose of decitabine. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: decitabine<br>* 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.<br>* Other names: Dacogen;|
| Experimental: 2<br> | Drug: decitabine<br>* 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.<br>* Other names: Dacogen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myelodysplastic Syndrome, Decitabine, Dacogen, MGI PHARMA, Inc.