Clinical trial NCT00002926: Combination Chemotherapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Myelodysplastic Syndrome or Acute Myelogenous Leukemia
Official title: Autologous Peripheral Blood Stem Cell Transplantation (PSCT) Versus a Second Intensive Consolidation Course After a Common Induction and Consolidation Course in Patients With Bad Prognosis Myelodysplastic Syndromes (MDS) and Acute Myelogenous Leukemia Secondary (SAML) to MDS of More Acute Than 6 Months Duration
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Leukemia
Myelodysplastic Syndromes
Keywords: secondary acute myeloid leukemia
refractory anemia
refractory anemia with ringed sideroblasts
refractory anemia with excess blasts
refractory anemia with excess blasts in transformation
chronic myelomonocytic leukemia
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
refractory cytopenia with multilineage dysplasia
childhood myelodysplastic syndromes
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 80
Sex: ALL
Minimum age (years): 16
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: Algemeen Ziekenhuis Middelheim
city: Brugge
country: Belgium
facility: A.Z. St. Jan
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Brussels
country: Belgium
facility: Hopital Universitaire Erasme
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Mont-Godinne Yvoir
country: Belgium
facility: Clinique Universitaire De Mont-Godinne
city: Zagreb
country: Croatia
facility: University Hospital Rebro
city: Prague
country: Czech Republic
facility: Institute of Hematology and Blood Transfusion
city: Lyon
country: France
facility: Hopital Edouard Herriot
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Hotel Dieu de Paris
city: Paris
country: France
facility: Hopital Necker
city: Duesseldorf
country: Germany
facility: Universitaetsklinik Duesseldorf
city: Essen
country: Germany
facility: Universitaetsklinik und Strahlenklinik - Essen
city: Heidelberg
country: Germany
facility: Medizinische Klinik und Poliklinik
city: Munich (Muenchen)
country: Germany
facility: Klinikum Grosshadern
city: Tuebingen
country: Germany
facility: Eberhard Karls Universitaet
city: Rome
country: Italy
facility: Ospedale San Eugenio
city: 's-Gravenhage
country: Netherlands
facility: Leyenburg Ziekenhuis
city: Amsterdam
country: Netherlands
facility: Vrije Universiteit Medisch Centrum
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Gasthuis
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Maastricht
country: Netherlands
facility: Academisch Ziekenhuis Maastricht
city: Nijmegen
country: Netherlands
facility: University Medical Center Nijmegen
city: Rotterdam
country: Netherlands
facility: University Hospital - Rotterdam Dijkzigt
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Zwolle
country: Netherlands
facility: Sophia Ziekehuis
city: Gothenburg (Goteborg)
country: Sweden
facility: Sahlgrenska University Hospital
city: Linkoping
country: Sweden
facility: University Hospital of Linkoping
city: Orebro
country: Sweden
facility: Orebro University Hospital
city: Stockholm
country: Sweden
facility: Huddinge University Hospital
city: Basel
country: Switzerland
facility: University Hospital
city: Bellinzona
country: Switzerland
facility: Ospedale San Giovanni
city: Bern
country: Switzerland
facility: Inselspital, Bern
city: Geneva
country: Switzerland
facility: Hopital Cantonal Universitaire de Geneva
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: St. Gallen
country: Switzerland
facility: Kantonsspital - St. Gallen
Study officials:
affiliation: Universitair Medisch Centrum St. Radboud - Nijmegen
name: Theo De Witte, MD, PhD
role: STUDY_CHAIR
References:
citation: de Witte T, Hagemeijer A, Suciu S, Belhabri A, Delforge M, Kobbe G, Selleslag D, Schouten HC, Ferrant A, Biersack H, Amadori S, Muus P, Jansen JH, Hellstrom-Lindberg E, Kovacsovics T, Wijermans P, Ossenkoppele G, Gratwohl A, Marie JP, Willemze R. Value of allogeneic versus autologous stem cell transplantation and chemotherapy in patients with myelodysplastic syndromes and secondary acute myeloid leukemia. Final results of a prospective randomized European Intergroup Trial. Haematologica. 2010 Oct;95(10):1754-61. doi: 10.3324/haematol.2009.019182. Epub 2010 May 21.