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
60 Years
N/A
Both
Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms
Trial Information
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
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Duration of overall survival
Safety Issue:
No
Principal Investigator
Pierre W. Wijermans, MD, PhD
Investigator Affiliation:
HagaZiekenhuis - Locatie Leyenburg
Authority:
United States: Federal Government
Study ID:
CDR0000256224
NCT ID:
NCT00043134
Start Date:
May 2002
Completion Date:
Related Keywords:
- Leukemia
- Myelodysplastic Syndromes
- Myelodysplastic/Myeloproliferative Neoplasms
- 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
- Neoplasms
- Leukemia
- Leukemia, Myelomonocytic, Chronic
- Myelodysplastic Syndromes
- Preleukemia
- Myeloproliferative Disorders
- Myelodysplastic-Myeloproliferative Diseases
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