Clinical trial NCT00043134: Low-Dose Decitabine Compared With Standard Supportive Care in Treating Older Patients With Myelodysplastic Syndrome
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Leukemia
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Neoplasms
Keywords: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 220
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility 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

Primary outcomes:
measure: Duration of overall survival
Secondary outcomes:
measure: Best response rate as measured by Cheson response criteria
measure: Overall progression-free survival
measure: Toxicity as assessed by CTC v2.0
measure: Quality of life as assessed by EORTC QLQ30
measure: Days in Hospital
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Innsbruck Universitaetsklinik
city: Salzburg
country: Austria
facility: St. Johanns-Spital
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Roeselare
country: Belgium
facility: H. Hartziekenhuis - Roeselaere.
city: Verviers
country: Belgium
facility: Centre Hospitalier Peltzer-La Tourelle
city: Zagreb
country: Croatia
facility: University Hospital Rebro
city: Prague
country: Czech Republic
facility: First Medical Clinic of Charles University Hospital
city: Prague
country: Czech Republic
facility: Institute of Hematology and Blood Transfusion
city: Berlin
country: Germany
facility: Charite University Hospital - Campus Virchow Klinikum
city: Braunschweig
country: Germany
facility: Staedtisches Klinikum Braunschweig
city: Bremen
country: Germany
facility: DIAKO Ev. Diakonie Krankenhaus gGmbH
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carus
city: Duisburg
country: Germany
facility: St. Johannes Hospital - Medical Klinik II
city: Eschweiler
country: Germany
facility: St. Antonius Hospital
city: Frankfurt
country: Germany
facility: Klinikum der J.W. Goethe Universitaet
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg
city: Freiburg
country: Germany
facility: Klinikum der Albert - Ludwigs - Universitaet Freiburg
city: Greifswald
country: Germany
facility: Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Ruprecht - Karls - Universitaet Heidelberg
city: Homburg
country: Germany
facility: Universitaetsklinikum des Saarlandes
city: Kaiserslautern
country: Germany
facility: Westpfalz-Klinikum GmbH
city: Leer
country: Germany
facility: Onkologische Schwerpunktpraxis - Leer
city: Luebeck
country: Germany
facility: Sana Kliniken Luebeck
city: Luedenscheid
country: Germany
facility: Kreiskrankenhaus Luedenscheid
city: Munich
country: Germany
facility: Klinikum der Universitaet Muenchen - Grosshadern Campus
city: Munich
country: Germany
facility: Staedtisches Krankenhaus Muenchen - Harlaching
city: Munich
country: Germany
facility: Klinikum Rechts Der Isar - Technische Universitaet Muenchen
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus
city: Tuebingen
country: Germany
facility: Southwest German Cancer Center at Eberhard-Karls-University
city: Villingen-Schwenningen
country: Germany
facility: Klinikum Der Stadt Villingen - Schwenningen
city: Wuerzburg
country: Germany
facility: Medizinische Poliklinik, Universitaet Wuerzburg
city: Florence
country: Italy
facility: Universita Degli Studi di Florence - Policlinico di Careggi
city: Lecce
country: Italy
facility: Azienda Ospedaliera Vito Fazzi
city: Pesaro
country: Italy
facility: Azienda Ospedale - d S. Salvatore
city: Rome
country: Italy
facility: Istituto Regina Elena
city: Rome
country: Italy
facility: Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore
city: 's-Gravenhage
country: Netherlands
facility: HagaZiekenhuis - Locatie Leyenburg
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Gasthuis
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Maastricht
country: Netherlands
facility: Academisch Ziekenhuis Maastricht
city: Nijmegen
country: Netherlands
facility: Universitair Medisch Centrum St. Radboud - Nijmegen
city: Basel
country: Switzerland
facility: Kantonsspital - Abteilung Onkologie
city: Ankara
country: Turkey
facility: Ibn-i Sina Hospital
city: Southampton
country: United Kingdom
facility: Royal South Hants Hospital
state: England
Study officials:
affiliation: HagaZiekenhuis - Locatie Leyenburg
name: Pierre W. Wijermans, MD, PhD
affiliation: University Hospital Freiburg
name: Michael Luebbert, MD
References:
citation: 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.