Use of Decitabine in Myelodysplastic Syndrome (MDS) Following Azacitidine (AZA) Failure

Study Overview
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Brief Summary
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The purpose of this study is to assess the response rate at 6 months in Myelodysplastic Syndrome (MDS) patients, Chronic Myelomonocytic Leukaemia (CMML-2) patients, and Acute Myeloid Leukaemia (AML) patients with up to 30% bone marrow blasts, treated with low-dose decitabine who have previously failed therapy with 5-azacitidine.

Official Title
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Use of Decitabine in Myelodysplastic Syndrome (MDS) Following Azacitidine (AZA) Failure

Conditions
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Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia, Myelodysplastic Syndrome

Intervention / Treatment
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* Drug: Decitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written signed informed consent. ≥18 years of age. Diagnosed MDS with 5% or more marrow blasts and IPSS risk intermediate 2 or high risk; or chronic myelomonocytic leukemia (CMML-2); or AML with 20-30% bone marrow blasts. Patients who have failed therapy with azacitidine. Performance status 0-2 (ECOG scale). Adequate hepatic (bilirubin < 1.5 X ULN or AST< 2.5 X ULN) and renal functions (creatinine <1.5 X ULN). Exclusion Criteria: Nursing and pregnant females. Females of childbearing potential and males not willing to practice an effective method of contraception whilst receiving decitabine and for 2 months after the last infusion. Patients with previous malignancy or concurrent malignancy. Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure and unstable angina pectoris. Ongoing oral corticosteroids are not permitted. However, use of corticosteroids (topical and inhaled) is permitted and prophylactic steroids are allowed for transfusion reactions. Patients who have received any investigational agent within the 30 days preceding the first dose of study drug. Patients who have received prior intensive combination chemotherapy or high-dose cytarabine (>/= 1g/m*2 per dose). (Prior biologic therapies, targeted therapies and single agent chemotherapy are allowed). Patients who have an active viral or bacterial infection. Note: No patient is allowed to enter the study unless infections have been fully treated and the patient has remained afebrile for 7 days without antibiotics. Patients who have concurrent autoimmune hemolytic anemia or immune thrombocytopenia. Patients who have previously been treated with decitabine. Patients who have known positive serology for HIV. Patients with a condition that may be unable to comply with the treatment and monitoring requirements of the study.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Decitabine<br> | Drug: Decitabine<br>* Patients will receive decitabine as a 20mg/m2 one hour intravenous infusion once daily on days 1 to 5 of a 4 week cycle.<br>* Other names: Dacogen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate in the efficacy-evaluable (EE) population |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 18 months | 
| Time to AML progression (for MDS and CMML-2 patients only) or death |  | 18 months | 
| Haematological improvement |  | 18 months | 
| Transfusion requirements |  | 18 months | 
| Cytogenetic response |  | 18 months | 
| Treatment related toxicity |  | Up until one month after last IMP dose |