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

Sponsored by:	European Organization for Research and Treatment of Cancer
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00043134

Purpose

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.

Condition	Intervention	Phase
Leukemia Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases	Drug: decitabine	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control
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

Resource links provided by NLM:

MedlinePlus related topics: Anemia Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: 5-Aza-2'-deoxycytidine

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Duration of overall survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Best response rate as measured by Cheson response criteria [ Designated as safety issue: No ]
Overall progression-free survival [ Designated as safety issue: No ]
Toxicity as assessed by CTC v2.0 [ Designated as safety issue: Yes ]
Quality of life as assessed by EORTC QLQ30 [ Designated as safety issue: No ]
Days in Hospital [ Designated as safety issue: No ]

Estimated Enrollment:	220
Study Start Date:	May 2002
Estimated Primary Completion Date:	May 2008 (Final data collection date for primary outcome measure)

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

Ages Eligible for Study:	60 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00043134

Show 46 Study Locations

Sponsors and Collaborators

European Organization for Research and Treatment of Cancer

Investigators

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

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

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 ID Numbers:	CDR0000256224, EORTC-06011, SUPERGEN-EORTC-06011, GMDSG-EORTC-06011, EudraCT-2005-002830
Study First Received:	August 5, 2002
Last Updated:	February 24, 2009
ClinicalTrials.gov Identifier:	NCT00043134 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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
myelodysplastic/myeloproliferative disease, unclassifiable

Study placed in the following topic categories:

Antimetabolites
Chronic Myelomonocytic Leukemia
Precancerous Conditions
Hematologic Diseases
Leukemia, Myelomonocytic, Chronic
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Myelodysplastic Syndromes
Anemia
Myeloproliferative Disorders
Decitabine
Leukemia, Myeloid

Refractory Anemia
Leukemia
Preleukemia
Anemia, Refractory
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasm Metastasis
Chronic Myelogenous Leukemia
Anemia, Refractory, with Excess of Blasts
Bone Marrow Diseases
Myelodysplastic-Myeloproliferative Diseases
Myelodysplastic Myeloproliferative Disease

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Disease
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Precancerous Conditions
Antineoplastic Agents
Hematologic Diseases
Leukemia, Myelomonocytic, Chronic
Myelodysplastic Syndromes
Myeloproliferative Disorders
Enzyme Inhibitors

Decitabine
Leukemia, Myeloid
Pharmacologic Actions
Leukemia
Preleukemia
Neoplasms
Pathologic Processes
Therapeutic Uses
Syndrome
Myelodysplastic-Myeloproliferative Diseases
Bone Marrow Diseases

ClinicalTrials.gov processed this record on September 10, 2009