Low-Dose Decitabine Compared With Standard Supportive Care in Treating Older Patients With Myelodysplastic Syndrome

Study Overview
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Brief Summary
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RATIONALE: Decitabine may help myelodysplasia cells develop into normal stem cells. It is not yet known if decitabine is more effective than standard supportive care in treating myelodysplastic syndrome. PURPOSE: Randomized phase III trial to compare the effectiveness of low-dose decitabine with that of standard supportive care in treating older patients who have myelodysplastic syndrome.

Detailed Description
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OBJECTIVES: Compare the efficacy of low-dose decitabine vs standard supportive care, in terms of overall survival, of elderly patients with myelodysplastic syndromes. Compare the response rate and progression-free survival of patients treated with these regimens. Determine the toxicity of decitabine in these patients. Assess the duration of hospitalization and number of blood transfusions in patients treated with these regimens. Assess the quality of life of patients treated with these regimens. OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to cytogenetic risk factors (good vs poor vs intermediate vs unknown), disease (primary myelodysplastic syndrome (MDS) vs secondary MDS), and participating center. Patients with a successful cytogenetic exam are also stratified according to overall International Prognostic Scoring System score (intermediate 1 vs intermediate 2 vs high risk). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive decitabine IV over 4 hours every 8 hours for 3 days. Treatment repeats every 6 weeks for 4-8 courses in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive standard supportive care. Quality of life is assessed at baseline, every 6 weeks during therapy, every 2 months for 1 year, and then every 3 months thereafter. Patients are followed every 2 months for 1 year and then every 3 months thereafter. PROJECTED ACCRUAL: A total of 220 patients (110 per treatment arm) will be accrued for this study within 2 years.

Official Title
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Intravenous Low-Dose Decitabine Versus Supportive Care in Elderly Patients With Primary Myelodysplastic Syndrome (MDS) (>10% Blasts or High-Risk Cytogenetics), Secondary MDS or Chronic Myelomonocytic Leukemia (CMML) Who Are Not Eligible for Intensive Therapy: An EORTC-German MDS Study Group Randomized Phase III Study

Conditions
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Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms

Intervention / Treatment
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* Drug: decitabine


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of primary or secondary myelodysplastic syndromes (MDS) Any FAB or WHO criteria cellular type allowed Bone marrow blast count on aspiration or biopsy of 1 of the following: No more than 10% with poor cytogenetic risk factors (defined as any numerical or structural abnormality of chromosome 7 and/or complex abnormalities) 11-20% 21-30% for patients with acute myeloid leukemia (AML) secondary to MDS (i.e., refractory anemia with excess blasts in transformation by FAB classification) Patients who failed the cytogenetic exam are allowed provided bone marrow blasts are at least 5% and/or 2-3 cytopenias are present No rapid progression towards full-blown AML No blast crisis of chronic myeloid leukemia No t(8;21) alone or in combination with other abnormalities Ineligible for intensive chemotherapy (e.g., cytarabine or an anthracycline) PATIENT CHARACTERISTICS: Age 60 and over Performance status WHO 0-2 Life expectancy Not specified Hematopoietic See Disease Characteristics Hepatic Bilirubin less than 1.5 times upper limit of normal (ULN) Hepatitis B surface antigen negative Renal Creatinine less than 1.5 times ULN Cardiovascular No severe cardiovascular disease No arrhythmias requiring chronic treatment No congestive heart failure No New York Heart Association class III or IV heart disease No symptomatic ischemic heart disease Other HIV negative No active uncontrolled infection No other malignancy within the past 3 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix within the past 2 years No prior or concurrent evidence of CNS or psychiatric disorders requiring hospitalization No psychological, familial, sociological, or geographical condition that would preclude study PRIOR CONCURRENT THERAPY: Biologic therapy More than 6 weeks since prior growth factors for primary MDS No concurrent antiangiogenic drugs (e.g., thalidomide) No concurrent interleukin, interferon, or anti-thymocyte globulin Chemotherapy See Disease Characteristics More than 6 weeks since prior hydroxyurea for primary MDS No other prior chemotherapy for MDS or AML Prior chemotherapy for solid tumors or lymphoma (resulting in secondary MDS) allowed Endocrine therapy No concurrent steroids (except as inhalation therapy) Radiotherapy Prior radiotherapy for solid tumors or lymphoma (resulting in secondary MDS) allowed Surgery Not specified Other More than 6 weeks since prior immunosuppressive agents for primary MDS No concurrent amifostine No concurrent cyclosporine No other concurrent experimental therapies

Ages Eligible for Study
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Minimum Age: 60 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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: decitabine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of overall survival |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best response rate as measured by Cheson response criteria |  |  | 
| Overall progression-free survival |  |  | 
| Toxicity as assessed by CTC v2.0 |  |  | 
| Quality of life as assessed by EORTC QLQ30 |  |  | 
| Days in Hospital |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic myelomonocytic leukemia, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, refractory anemia, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, refractory anemia with ringed sideroblasts, refractory cytopenia with multilineage dysplasia, secondary myelodysplastic syndromes, atypical chronic myeloid leukemia, BCR-ABL negative, myelodysplastic/myeloproliferative neoplasm, unclassifiable