A Remission Induction Therapy and Risk-Oriented Postremission Strategy for Adult Acute Myelogenous Leukemia (AML) - Full Text View

Sponsored by:	Northern Italy Leukemia Group
Information provided by:	Northern Italy Leukemia Group
ClinicalTrials.gov Identifier:	NCT00495287

Purpose

The study was set up to assess:

Standard-dose versus high-dose remission induction therapy. A standard ICE chemotherapy vs sequential high-dose cytarabine, with appropriate supportive/prophylactic measures, followed by morphological, cytogenetic and molecular monitoring of remission.
A risk-oriented postremission therapy: HR patients will be electively submitted to allogeneic stem cell transplantation (allo-SCT), whenever possible (related/unrelated donor/cord blood; ablative/non-ablative conditioning according to national and local protocols and guidelines). Provided sufficient blood stem cells were previously collected (>2x10e6/kg CD34+ cells), SR patients and HR patients excluded from allo-SCT and aged 65 years or less will be randomized to: myeloablative autologous blood stem cell transplantation vs non-myeloablative, multicycle, autologous blood stem cell-supported high-dose cytarabine-based therapy.
- HR/SR patients unable to be randomized because of inadequate blood stem cell yield will receive intermediate-dose consolidation; patients aged >65 years will be treated with age-adapted therapy.

Condition	Intervention	Phase
Acute Myelogenous Leukemia	Drug: cytosine arabinoside	Phase III

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

Drug Information available for: Cytarabine Cytarabine hydrochloride Etoposide Idarubicin Idarubicin hydrochloride Etoposide phosphate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Official Title:	Phase III Trial in AML Comparing Standard-Dose vs High-Dose Remission Induction and, Within a Risk-Oriented Postremission Strategy, Autologous Blood Stem Cell Transplantation vs Blood Stem Cell-Supported Multicycle High-Dose Program

Further study details as provided by Northern Italy Leukemia Group:

Primary Outcome Measures:

Remission induction (R1): Complete remission (CR) rate after cycle 1 [ Time Frame: 30 days after beginning chemotherapy. ] [ Designated as safety issue: Yes ]
Remission consolidation (R2): Length of remission (DFS, disease-free survival) [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

R1: CR with incomplete hematological recovery [ Time Frame: 30 days after beginning chemotherapy ] [ Designated as safety issue: No ]
R1:Complete cytogenetic remission [ Time Frame: 30 days after beginning chemotherapy ] [ Designated as safety issue: No ]
R1: Treatment-related death (TRD) [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]
R2: Overall survival (OS) [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
Remission duration and cumulative incidence of relapse [ Time Frame: 5 years ] [ Designated as safety issue: No ]
Treatment-related death [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
Quality of Life [ Time Frame: 1 year and 3 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	500
Study Start Date:	November 2006
Estimated Study Completion Date:	December 2011
Estimated Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Active Comparator Remission induction arm A is with conventional chemotherapy cycle ("ICE": idarubicin, standard-dose cytarabine, etoposide)	Drug: cytosine arabinoside Arm A: use of standard-dose cytosine arabinoside (100 mg/m2/bd iv. on days 1-7) in association with idarubicin and etoposide. Arm B: use of high-dose cytosine arabinoside (1000-2000 mg/m2/bd according to age +/-65 years iv. on days 1-2 and 8-9) in association with idarubicin.
B: Experimental Remission induction therapy with high-dose cytarabine sequential regimen (HD-Ara-C, idarubicin)	Drug: cytosine arabinoside Arm A: use of standard-dose cytosine arabinoside (100 mg/m2/bd iv. on days 1-7) in association with idarubicin and etoposide. Arm B: use of high-dose cytosine arabinoside (1000-2000 mg/m2/bd according to age +/-65 years iv. on days 1-2 and 8-9) in association with idarubicin.

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Eligibility

Ages Eligible for Study:	16 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion criteria (Random 1):

Age 16+ years
Diagnosis of untreated (or only hydroxyurea/cyclophosphamide) acute myelogenous leukemia (AML, including myeloid sarcoma) or high-risk myelodysplasia (RAEB-2), either de novo or following an antecedent hematological disorder, or secondary to chemo-radiotherapy for other cancer
Signed informed consent
Adequate sampling for full cytological, cytochemical, cytogenetic and immunobiological disease characterization by revised FAB, EGIL and WHO criteria
ECOG performance status 0-2 or reversible ECOG 3 score following intensive care of complications.

Exclusion criteria:

Diagnosis of acute promyelocytic leukemia
Pre-existing, uncontrolled pathology such as cardiac disease (congestive/ischemic, acute myocardial infarction within the past 3 months, untreatable arrythmias, NYHA classes III and IV), severe liver disease with serum bilirubin >3 mg/dL and/or ALT >3 x upper normal limit (unless attributable to AML), kidney function impairment with serum creatinine >2 mg/dL (unless attributable to AML), and severe neuropsychiatric disorder that impairs the patient's ability to understand and sign the informed consent, or to cope with the intended treatment plan
Known HIV positive serology
Other active hematological or non-hematological cancers with life expectancy <1 year
Pregnancy (fertile women will be advised not to become pregnant while on treatment; and male patients to adopt contraceptive methods)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00495287

Contacts

Contact: Roberto Marchioli, MD	+39 0872570250	marchioli@negrisud.it
Contact: Giovanna Borrelli, Dr Sci	+39 0872570324	borrelli@negrisud.it

Locations

Italy, AL
Dipartimento di Ematologia e Medicina Trasfusionale - Azienda Osp. Nazionale Santi Antonio e Biagio e Cesare Arrigo	Recruiting
Alessandria, AL, Italy
Principal Investigator: Alessandro Levis, MD
Sub-Investigator: Flavia Salvi, MD
Sub-Investigator: Lorella Depaoli, MD
Italy, BG
USC Ematologia Ospedali Riuniti di Bergamo	Recruiting
Bergamo, BG, Italy
Principal Investigator: Renato Bassan, MD
Sub-Investigator: Tamara Intermesoli, MD
Sub-Investigator: Elena Oldani, Dr. Biol Sci
Sub-Investigator: Federica Delaini, Dr. Biol Sci
Sub-Investigator: Orietta Spinelli, Dr. Biol Sci
Sub-Investigator: Vittoria Guerini
Italy, CN
S.C. Ematologia - Azienda Ospedaliera S.Croce e Carle	Recruiting
Cuneo, CN, Italy
Principal Investigator: Daniele Mattei, MD
Sub-Investigator: Andrea Gallamini, MD
Italy, FI
Ematologia - AOU Careggi	Recruiting
Firenze, FI, Italy
Principal Investigator: Alberto Bosi, MD
Sub-Investigator: Franco Leoni, MD
Sub-Investigator: Giacomo Gianfaldoni, MD
Sub-Investigator: Francesco Mannelli, MD
Sub-Investigator: Alessandro Vannucchi, MD
Italy, MI
Ematologia Centro TMO - Fondazione IRCSS Ospedale Maggiore	Not yet recruiting
Milano, MI, Italy
Principal Investigator: Giorgio Lambertenghi-Deliliers, MD
Sub-Investigator: Agostino Cortelezzi, MD
Sub-Investigator: Maria Cristina Pasquini, MD
Sub-Investigator: Nicola Fracchiolla, MD
Sub-Investigator: Claudio Annaloro, MD
Sub-Investigator: Angelo Gardellini, MD
Sub-Investigator: Kathrin Von Hohenstaufen, MD
Ematologia e TMO - Ospedale San Raffaele	Recruiting
Milano, MI, Italy
Principal Investigator: Fabio Ciceri, MD
Sub-Investigator: Massimo Bernardi, MD
Sub-Investigator: Michela Tassara, MD
Sub-Investigator: Alessandro Crotta, MD
Ematologia - TMO - Ospedale San Gerardo	Recruiting
Monza, MI, Italy
Principal Investigator: Enrico Pogliani, MD
Sub-Investigator: Elisabetta Terruzzi, MD
Sub-Investigator: Matteo Parma, MD
Sub-Investigator: Monica Fumagalli, MD
Sub-Investigator: Luisa Verga, MD
Italy, to
Ematologia 2 - Osp. Molinette San Giovanni Battista	Recruiting
Torino, to, Italy
Principal Investigator: Eugenio Gallo, MD
Sub-Investigator: Filippo Mormont, MD
Sub-Investigator: Ernesta Audisio, MD
Sub-Investigator: Stefano D'Ardia, MD

Sponsors and Collaborators

Northern Italy Leukemia Group

Investigators

Principal Investigator:

Renato Bassan, MD

Ospedali Riuniti di Bergamo USC Ematologia

More Information

Related Info This link exits the ClinicalTrials.gov site

Responsible Party:	Coordinator, Northern Italy Leukemia Group ( Renato Bassan, MD )
Study ID Numbers:	NILG-AML 02/06
Study First Received:	July 2, 2007
Last Updated:	May 22, 2008
ClinicalTrials.gov Identifier:	NCT00495287
Health Authority:	Italy: Ministry of Health

Keywords provided by Northern Italy Leukemia Group:

Acute myelogenous leukemia
Adult patients
Cytogenetic risk class
Clinico-cytogenetic risk model
Risk-oriented therapy

Study placed in the following topic categories:

Leukemia
Idarubicin
Acute myelogenous leukemia
Acute myeloid leukemia, adult
Leukemia, Myeloid

Leukemia, Myeloid, Acute
Etoposide phosphate
Etoposide
Acute myelocytic leukemia
Cytarabine

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents

Physiological Effects of Drugs
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Therapeutic Uses

ClinicalTrials.gov processed this record on January 16, 2009