RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.

PURPOSE: Randomized phase III trial to compare the effectiveness of peripheral stem cell transplantation with high-dose cytarabine in treating patients with myelodysplastic syndrome or acute myelogenous leukemia.

Condition	Treatment or Intervention	Phase
Myelodysplastic Syndromes Myeloid Leukemia Refractory Anemia Refractory Cytopenia	Drug: cytarabine  Drug: etoposide  Drug: idarubicin  Procedure: allogeneic bone marrow transplantation  Procedure: biological response modifier therapy  Procedure: bone marrow ablation with stem cell support  Procedure: bone marrow transplantation  Procedure: chemotherapy  Procedure: peripheral blood stem cell transplantation	Phase III

Further Study Details: 

OBJECTIVES:

• Assess the value of autologous peripheral stem cell transplantation versus high dose cytarabine (Ara-C) performed after a common induction and consolidation course in patients with poor prognosis myelodysplastic syndromes (MDS) or acute myelogenous leukemia secondary to MDS.
• Compare the disease free survival and overall survival of patients who reached complete recovery according to the presence of an HLA-identical donor.
• Monitor cytogenetic and clonal remission after intensive antileukemic therapy including stem cell transplantation.
• Monitor residual disease and the hematopoietic clonal status of autologous peripheral blood stem cells mobilized after one consolidation course.
• Assess recovery time of granulocyte and platelet counts following each treatment step.

OUTLINE: Induction treatment with idarubicin on days 1,3,5; Ara-C from days 1 through 10; etoposide on days 1 through 5. On day 28 there will be assessment of responses. If there is at least partial response, the cycle will repeat the induction course for another 28 days. There is peripheral blood stem cell collection and cryopreservation following family HLA-typing. If there is no HLA match, then those who remained in remission after these consolidation courses will be randomized to either peripheral blood stem cell transplantation or HiDAC treatment.

PROJECTED ACCRUAL: 80 patients will be entered per year.

Ages Eligible for Study:  16 Years   -   60 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Pathological confirmation of one of the following:
• Untreated refractory anemia with excess blasts (RAEB) in transformation
• RAEB with greater than 10% blasts cells in the bone marrow
• Other myelodysplastic syndromes
• Profound cytopenias
• Acute myelogenous leukemia (AML) supervening after overt myelodysplastic syndromes (MDS) of more than 6 months duration
• No blast crisis of chronic myeloid leukemia
• No leukemias supervening after other myeloproliferative disease
• No leukemias supervening after overt MDS of less than 6 months duration
• The following are allowed:
• Secondary acute leukemias following Hodgkin's disease or other malignancies
• Secondary leukemias following exposure to alkylating agents or radiation

PATIENT CHARACTERISTICS: Age:

• 16-60

Performance status:

• WHO 0-2

Hematopoietic:

• If RAEB, blasts cells of greater than 10% in bone marrow
• Neutrophil count less than 5,000 or Platelet count less than 200,000
• Chronic myelomonocytic leukemia (CMML) with greater than 5% blasts cells in bone marrow, or CMML with neutrophil count greater than 160,000 or monocyte count greater than 2,600

Hepatic:

• Bilirubin no greater than 1.5 times normal

Renal:

• Creatinine no greater than 1.5 times normal

Cardiovascular:

• No patients with severe heart failure requiring diuretics or an ejection fraction of less than 50%

Neurological:

• No severe concomitant neurological disease

PRIOR CONCURRENT THERAPY: Biologic therapy:

• No treatments within the past 4 weeks of:
• Biological response modifiers AND/OR
• Low dose Ara-C

Chemotherapy:

• No prior intensive treatment for MDS or AML

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior treatment for MDS or AML

Surgery:

• Not specified

Belgium
      A.Z. St. Jan, Brugge,  8000,  Belgium
      Algemeen Ziekenhuis Middelheim, Antwerp,  2020,  Belgium
      Clinique Universitaire De Mont-Godinne, Mont-Godinne Yvoir,  5530,  Belgium
      Cliniques Universitaires Saint-Luc, Brussels,  1200,  Belgium
      Hopital Universitaire Erasme, Brussels,  1070,  Belgium
      Institut Jules Bordet, Brussels,  1000,  Belgium
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium
      Universitair Ziekenhuis Antwerpen, Edegem,  B-2650,  Belgium
Croatia
      University Hospital Rebro, Zagreb,  10000,  Croatia
Czech Republic
      Institute of Hematology and Blood Transfusion, Prague,  128 20,  Czech Republic
France
      Centre Antoine Lacassagne, Nice,  06189,  France
      Hopital Edouard Herriot, Lyon,  69437,  France
      Hopital Necker, Paris,  75743,  France
      Hotel Dieu de Paris, Paris,  75181,  France
Germany
      Eberhard Karls Universitaet, Tuebingen,  D-72076,  Germany
      Klinikum Grosshadern, Munich (Muenchen),  D-81377,  Germany
      Medizinische Klinik und Poliklinik, Heidelberg,  92093-0671,  Germany
      Universitaetsklinik Duesseldorf, Duesseldorf,  D-40225,  Germany
      Universitaetsklinik und Strahlenklinik - Essen, ESSEN,  D-45122,  Germany
Italy
      Ospedale San Eugenio, Rome,  00144,  Italy
Netherlands
      Academisch Medisch Centrum, Amsterdam,  1105 AZ,  Netherlands
      Academisch Ziekenhuis Maastricht, Maastricht,  6202 AZ,  Netherlands
      Erasmus Medical Center, Rotterdam,  3075 EA,  Netherlands
      Leiden University Medical Center, Leiden,  2300 CA,  Netherlands
      Leyenburg Ziekenhuis, 's-Gravenhage,  2545 CH,  Netherlands
      Onze Lieve Vrouwe Gasthuis, Amsterdam,  1091 HA,  Netherlands
      Sophia Ziekehuis, Zwolle,  8000 GK,  Netherlands
      University Hospital - Rotterdam Dijkzigt, Rotterdam,  3000 CA,  Netherlands
      University Medical Center Nijmegen, Nijmegen,  NL-6500 HB,  Netherlands
      Vrije Universiteit Medisch Centrum, Amsterdam,  1001HV,  Netherlands
Sweden
      Huddinge University Hospital, Stockholm,  SE-141 86,  Sweden
      Orebro University Hospital, OREBRO,  70185,  Sweden
      Sahlgrenska University Hospital, Gothenburg (Goteborg),  S-413 45,  Sweden
      University Hospital of Linkoping, Linkoping,  S-581 85,  Sweden
Switzerland
      Centre Hospitalier Universitaire Vaudois, Lausanne,  CH-1011,  Switzerland
      Hopital Cantonal Universitaire de Geneva, Geneva,  CH-1211,  Switzerland
      Inselspital, Bern, Bern,  CH-3010,  Switzerland
      Kantonsspital - St. Gallen, St. Gallen,  CH-9007,  Switzerland
      Ospedale San Giovanni, Bellinzona,  CH-6500,  Switzerland
      University Hospital, Basel,  CH-4031,  Switzerland

Study chairs or principal investigators

Theo De Witte, MD, PhD,  Study Chair,  University Medical Center Nijmegen   

Study ID Numbers:  CDR0000065336; EORTC-06961
Record last reviewed:  March 2003
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002926
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08