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

April 10, 2010 updated by: European Organisation for Research and Treatment of Cancer - EORTC

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Anticipated)

220

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Innsbruck, Austria, A-6020
        • Innsbruck Universitaetsklinik
      • Salzburg, Austria, A-5020
        • St. Johanns-Spital
  • Belgium
      • Brussels, Belgium, 1000
        • Institut Jules Bordet
      • Leuven, Belgium, B-3000
        • U.Z. Gasthuisberg
      • Roeselare, Belgium, 8800
        • H. Hartziekenhuis - Roeselaere.
      • Verviers, Belgium, B-4800
        • Centre Hospitalier Peltzer-La Tourelle
  • Croatia
      • Zagreb, Croatia, 41000
        • University Hospital Rebro
  • Czech Republic
      • Prague, Czech Republic, 128 20
        • Institute of Hematology and Blood Transfusion
      • Prague, Czech Republic, 128 08
        • First Medical Clinic of Charles University Hospital
  • Germany
      • Berlin, Germany, D-13353
        • Charite University Hospital - Campus Virchow Klinikum
      • Braunschweig, Germany, G-38114
        • Staedtisches Klinikum Braunschweig
      • Bremen, Germany, 28239
        • DIAKO Ev. Diakonie Krankenhaus gGmbH
      • Dresden, Germany, D-01307
        • Universitätsklinikum Carl Gustav Carus
      • Duisburg, Germany, D-47166
        • St. Johannes Hospital - Medical Klinik II
      • Eschweiler, Germany, DOH-52249
        • St. Antonius Hospital
      • Frankfurt, Germany, D-60590
        • Klinikum der J.W. Goethe Universitaet
      • Freiburg, Germany, D-79106
        • Universitaetsklinikum Freiburg
      • Freiburg, Germany, DOH-79104
        • Klinikum der Albert - Ludwigs - Universitaet Freiburg
      • Greifswald, Germany, D-17487
        • Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet
      • Hannover, Germany, D-30625
        • Medizinische Hochschule Hannover
      • Heidelberg, Germany, D-69117
        • Ruprecht - Karls - Universitaet Heidelberg
      • Homburg, Germany, D-66421
        • Universitaetsklinikum des Saarlandes
      • Kaiserslautern, Germany, D-67653
        • Westpfalz-Klinikum GmbH
      • Leer, Germany, D-26789
        • Onkologische Schwerpunktpraxis - Leer
      • Luebeck, Germany, 23560
        • Sana Kliniken Luebeck
      • Luedenscheid, Germany, 58515
        • Kreiskrankenhaus Luedenscheid
      • Munich, Germany, D-81377
        • Klinikum der Universitaet Muenchen - Grosshadern Campus
      • Munich, Germany, D-81675
        • Klinikum Rechts der Isar - Technische Universitaet Muenchen
      • Munich, Germany, D-81545
        • Staedtisches Krankenhaus Muenchen - Harlaching
      • Stuttgart, Germany, D-70376
        • Robert-Bosch-Krankenhaus
      • Tuebingen, Germany, D-72076
        • Southwest German Cancer Center at Eberhard-Karls-University
      • Villingen-Schwenningen, Germany, D-78054
        • Klinikum Der Stadt Villingen - Schwenningen
      • Wuerzburg, Germany, D-97070
        • Medizinische Poliklinik, Universitaet Wuerzburg
  • Italy
      • Florence, Italy, 50134
        • Universita Degli Studi di Florence - Policlinico di Careggi
      • Lecce, Italy, 73100
        • Azienda Ospedaliera Vito Fazzi
      • Pesaro, Italy, I-61100
        • Azienda Ospedale - d S. Salvatore
      • Rome, Italy, 00161
        • Istituto Regina Elena
      • Rome, Italy, 00168
        • Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore
  • Netherlands
      • 's-Gravenhage, Netherlands, 2545 CH
        • HagaZiekenhuis - Locatie Leyenburg
      • Amsterdam, Netherlands, 1091 HA
        • Onze Lieve Vrouwe Gasthuis
      • Leiden, Netherlands, 2300 CA
        • Leiden University Medical Center
      • Maastricht, Netherlands, 6202 AZ
        • Academisch Ziekenhuis Maastricht
      • Nijmegen, Netherlands, NL-6500 HB
        • Universitair Medisch Centrum St. Radboud - Nijmegen
  • Switzerland
      • Basel, Switzerland, 4031
        • Kantonsspital - Abteilung Onkologie
  • Turkey
      • Ankara, Turkey, 06100
        • Ibn-i Sina Hospital
  • United Kingdom
    • England
      • Southampton, England, United Kingdom, SO14 0YG
        • Royal South Hants Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Duration of overall survival

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC

Investigators

  • Pierre W. Wijermans, MD, PhD, HagaZiekenhuis - Locatie Leyenburg
  • Michael Luebbert, MD, University Hospital Freiburg

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

  • WijerMans P, Suciu S, Baila L, et al.: Low dose decitabine versus best supportive sare in elderly patients with intermediate or high risk MDS not eligible for intensive chemotherapy: final results of the randomizedpPhase III study (06011) of the EORTC Leukemia and German MDS Study Groups. [Abstract] Blood 112 (11): A-226, 2008.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2002

Primary Completion (Anticipated)

May 1, 2008

Study Registration Dates

First Submitted

August 5, 2002

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

April 13, 2010

Last Update Submitted That Met QC Criteria

April 10, 2010

Last Verified

April 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000256224
  • EORTC-06011
  • SUPERGEN-EORTC-06011
  • GMDSG-EORTC-06011
  • EudraCT-2005-002830

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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