An Efficacy and Safety Study of Decitabine in Participants With Myelodysplastic Syndrome (MDS)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the response rate of decitabine in previously treated and untreated Taiwanese participants with Myelodysplastic Syndrome (MDS - a disease associated with decreased production of blood cells, blood cells are produced but do not mature normally).

Detailed Description
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This is an open-label (a medical research study in which participants and researchers are told which treatments the participants are receiving, unblinded), multi-center (when more than 1 hospital or medical school team work on a medical research study), single-arm study of decitabine. The study will consist of 5 phases: Pre-treatment phase (before 30 days of first dose), Treatment phase (consist of 8 cycles, each cycle of 28 days), End-of-treatment phase (consist of 30-42 days after the last dose of cycle 8, or at time of discontinuation), Extension phase (1 cycle of 4 weeks) and Post-study phase or follow-up phase (every 2 months until 1 year, lost to follow-up or death). Participants who achieve a complete remission (when a medical problem gets better or goes away at least for a while) will be treated for at least 2 more cycles after first documentation of complete response (CR), after which treatment can be discontinued. Decitabine in a dose of 20 milligram per square meter (mg per m^2) will be administered intravenously over 1 hour infusion, 1 hour, once daily for 5 consecutive days of a 28 days cycle up to 8 cycles or continued until disease progression or unacceptable toxicity. The primary objective is to evaluate the best response rate (complete response and partial response). Participants' safety will be monitored throughout the study.

Official Title
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A Phase II Multi-center Study of 5-AZA-2'-Deoxycytidine (Decitabine) Single Agent in Taiwanese Patients With Myelodysplastic Syndrome (MDS)

Conditions
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Myelodysplastic Syndrome

Intervention / Treatment
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* Drug: Decitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with documented pathological (bone marrow, no longer than 30 days before first dosing in study) evidence of Myelodysplastic syndromes (MDS) or of chronic myelomonocytic leukemia (CMML) by World health organisation classification Participants with international prognostic scoring system (IPSS) score equal to 0.5 or more (only for participants for whom IPSS is applicable) Participants with an Eastern oncology cooperative group (ECOG) performance status of 0-2 Participants with adequate hepatic (liver) and renal (kidney) function as measured by pre-treatment laboratory criteria within 21 days of starting treatment with decitabine Participants must have recovered from toxic effects of previous therapy and not receiving any chemotherapy for a minimum of 4 weeks (6 weeks if the participants has been treated with a nitrosoureas) before to the first dose of study drug Exclusion Criteria: Participants with a diagnosis of acute myeloid leukemia (AML) (greater than 30 percent bone marrow blasts) Participants with AML with multilineage dysplasia (abnormal development or cell growth) following MDS (20-30 percent bone marrow blasts) can be enrolled. For these latter participants an observation period of 1 month is necessary to exclude those participants with rapid progression to full blown AML Participants with previous treatment with azacitadine or decitabine or hematopoietic stem cell transplantation less than 1 year prior to study enrollment Participants with past history of malignancy and received any treatment for this before malignancy within the last 3 years, except for superficial bladder cancer, basal cell or squamous cell carcinoma of the skin, cervical intraepithelial neoplasia (CIN) or prostate intraepithelial neoplasia (PIN) Participants with known hepatitis B (surface antigen-positive) or active hepatitis C infection

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>Decitabine 20 milligram per square meter (mg per m^2) will be administered intravenous (into a vein) infusion (a fluid or a medicine delivered into a vein by way of a needle) over 1 hour, once daily for 5 consecutive days of a 28 days cycle up to 8 cycles or continued until disease progression or unacceptable toxicity. | Drug: Decitabine<br>* Decitabine 20 mg per m^2 will be administered intravenous infusion over 1 hour, once daily for 5 consecutive days of a 28 days cycle up to 8 cycles or continued until disease progression or unacceptable toxicity.<br>* Other names: 5-aza-2'-deoxycytidine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Response | Percentage of participants with response: complete response (CR) or partial response (PR) according to International Working Group (IWG) 2006 criteria was evaluated. CR in bone marrow is defined as<=to 5% myeloblasts with normal maturation of all cell lines and persistent dysplasia was noted in peripheral blood hemoglobin >=11 gram (g) per deciliter (dl), platelets >=100*10^9 liter (l), neutrophils >=1.0*10^9 l, Blasts 0%. Partial response is defined as all CR criteria if abnormal before treatment except: bone marrow blasts decreased by >=50% over pre-treatment but still >=5%. | Day 1 of Cycle 2, 4, 6, 8; each Cycle of 28 days and End of treatment (30-42 days after Cycle 8 or early withdrawal) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Hematologic Treatment Response | Hematologic treatment response was assessed as per IWG 2006 criteria. This is measured in erythroid(HI-E), platelet(HI-P) and neutrophil(HI-N) lineages. HI-E response(pre-treatment<11 gram per deciliter [g/dl]):hemoglobin increase by>=1.5 g/dl and relevant reduction in RBC transfusions by 4 RBC transfusions/8week. HI-P response (pre-treatment<100*109/l):absolute increase of >=30*10^9/l for participants starting with>20*10^9/l and increase from <20*10^9/l to>20*10^9/l and by at least 100%. HI-N response (pre-treatment<1.0*10^9/l): at least 100% increase and an absolute increase >0.5*10^9/l. | Day 1 of Cycle 1, 2, 3, 4, 5, 6, 7 and 8, each Cycle of 28 days and End of treatment (30-42 days after Cycle 8 or early withdrawal) | 
| Percentage of Participants With Cytogenetic Response | Cytogenetic responses was assessed as per IWG 2006 criteria which define complete response as disappearance of the chromosomal abnormality without appearance of new ones and partial response as at least 50 percent reduction of the chromosomal abnormality. | Day 1 of Cycle 2, 4, 6, 8; each Cycle of 28 days and End of treatment (30-42 days after Cycle 8 or early withdrawal) | 
| Time to Acute Myeloid Leukemia (AML) Progression or Death | Time to AML is defined as greater than 30 percent of blasts in bone marrow or the time to death was calculated from the date of treatment start until disease progression to AML or until death, which ever occurred first. Participants who were still alive and did not progress to AML were censored at the moment of last visit. | Start of treatment until disease progression or death (whichever occur first) or up to 736 days | 
| Overall Survival | Overall survival was defined as the time from the date of treatment start until death (whatever the cause). It was calculated from Kaplan-Meier estimates. Participants still alive were censored at the moment of last visit or contact. | Start of treatment until disease progression or death (whichever occur first) or up to 736 days | 
| Percentage of Participants With Transfusion Dependency | Transfusion requirements for both red blood cells as well as platelets were recorded for each participant. | 8 weeks before first dose until disease progression or death (whichever occur first) or up to 736 days | 
| Percentage of Participants With Transfusion Independency | Transfusion independent participants were calculated from all the participants who required transfusion in the duration of 8 weeks before first dose until disease progression or death or up to 736 days. Transfusion independence was defined as lack of requirement for transfusions for at least 8 weeks. | 8 weeks before first dose and 736 days of treatment | 
| Duration for Hospitalization | Duration of hospitalization was calculated for each participant, using the sum of all hospital days by subtracting the date of discharge from the date of admission. | Cycle 1 up to Cycle 8, each cycle of 28 days. | 
| Number of Events Which Led to Hospitalization | The events (reasons) for hospitalizations such as infection, transfusion, acute choleycystitis, allergic transfusion reaction, dyspnoea with right pleural effusion, febrile neutropenia, fever, for decitabine, Myelodysplastic Syndrome (MDS) hematuria, paronychia, pneumonia, heart failure, peri-anal abscess (PAA), pancytopenia,fluctuated neutropenia fever, right dorsal foot cellulitis, Right lower (Rt.Lw) lung pneumonia with impending respiratory (resp) failure, Serious adverse event (SAE)+schedule hospitalization for decitabine, septic shock and not available were reported. | Start of treatment until disease progression or death or up to Cycle 8, each cycle of 28 days | 
| Quality of Life Assessment | The quality of life was assessed by the questionnaire QLQ C-30 designed by European Organization for the Research and Treatment of Cancer (EORTC). EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer participants. Most questions used 4-point scale (1=Not at All' to 4=Very Much') and 2 questions: Q29 on overall health and Q30 on overall quality of life uses 7-point scale ranging from 1=Very Poor to 7=Excellent. Higher score indicates better quality of life. | Day 1 of Cycle 1 and Cycle 8 (each cycle of 28 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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5-aza-2'-deoxycytidine, decitabine, dacogen, Myelodysplastic Syndrome