Intravenous low-dose decitabine versus supportive care in elderly patients withprimary Myelodysplastic Syndrome (MDS) (>10 % blasts or high-risk cytogenetics),secondary MDS or Chronic Myelomonocytic Leukemia (CMML) who are noteligible for intensive therapy: an EORTC-German MDS Study Group randomizedphase III study
- Conditions
- The myelodysplastic syndrome (MDS) comprises a heterogenous group of hematopoietic stem cell disorders. - quantitative and morphologic abnormalities of bone marrow and peripheral blood cells - chromosomal abnormalities in about half of the cases: deletions , numerical aberrations and balanced translocations similar to those found in acute myeloid leukemia (AML).- DNA hypermethylation, mutations of ras genes, and loss of heterozygosity at tumor suppressor genes.MedDRA version: 8.0Level: HLTClassification code 10028536
- Registration Number
- EUCTR2005-002830-36-CZ
- Lead Sponsor
- European Organisation for Research and Treatment of Cancer
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 220
? Patients aged 60 years and older with either:
? primary MDS without any pretreatment
? primary MDS pretreated with either growth factors, immunosuppressive
agents or hydroxyurea. These drugs have to be stopped > 6 weeks before
randomisation.
? secondary MDS (previous radio-/chemotherapy for solid tumors or
lymphoma)
and based on a BM aspiration or, in case of dry tap, on a BM biopsy, with either:
? Bone marrow blast count of 11-20%,
? Bone marrow blast count of = 10% with poor cytogenetics: any numerical or
structural abnormality of chromosome 7 and/or complex abnormalities (= 3
abnormalities)
? Bone marrow blast count of 21-30% (AML from MDS according to WHO
proposal, RAEB-t according to FAB) in centers not participating in the AML
elderly study of the EORTC. For these patients an observation period of one
month is necessary to exclude those patients with a rapid progression
towards full-blown AML.
NB: - The BM sample should be done within 3 weeks prior to randomization, the cytogenetics
examination should be done within 8 weeks prior to randomization, the blood sample
should be done within 1 week prior to randomization.
- Patients for whom the cytogenetic examination was unsuccesful (this means that
cytogenetic examination has been performed on BM or on blood material, but that the
result was considered as a failure; ex: NN with < 10 mitoses), may be included in this
trial, provided that the % of BM blasts is =5 % and/or 2-3 cytopenias are present.
? Absence of blast crisis of chronic myeloid leukemia.
? Absence of t(8;21), alone or in combination with other abnormalities
? Absence of pretreatment for MDS or AML with chemotherapy other than hydroxyurea.
? Absence of active malignancy in previous three years with the exception of basal or squamous
cell skin cancer or cervical carcinoma in situ within two years of study registration.
? Ineligible for intensive chemotherapy (ex: an anthracycline and Ara-C)
? Performance status according to the WHO scale: 0, 1 or 2.
? Adequate renal and liver function: creatinine and bilirubin < 1.5 times the upper limit of normal.
? Absence of severe cardiovascular disease, i.e., arrhythmias requiring chronic treatment,
congestive heart failure (NYHA Class III or IV) or symptomatic ischemic heart disease, where
New-York Heart Association (NYHA)
Class III: marked limitation of activity; less than ordinary activity results in symptoms
Class IV: unable to carry on any physical activity without discomfort; symptoms at rest.
? HIV negative and HBsAg negative.
? Absence of active uncontrolled infection.
? No prior history or current evidence of central nervous system and psychiatric disorders
requiring hospitalization.
? Absence of any psychological, familial, sociological or geographical condition potentially
hampering compliance with the study protocol and follow-up schedule; those conditions should
be discussed with the patient before registration in the trial.
? Before patient randomization, signed written informed consent must be given according to ICH
GCP, and national/local regulations.
N.B. Patients can be randomized only once in this trial.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
Not provided
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The main goal of this open-label randomized phase III trial is to assess the efficacy, toxicity,<br>duration of hospitalization and quality of life of low dose Decitabine versus supportive care in<br>elderly patients with a myelodysplastic syndrome.<br>;Secondary Objective: As part of the translational research:<br>Unravel the cellular and molecular mechanisms by which <br>the drug is active in MDS, with the long-term aim of improving treatment by defining rational drug<br>combinations and schedules based upon a better understanding of the effect of Decitabine.;Primary end point(s): ? Overall survival
- Secondary Outcome Measures
Name Time Method