A Remission Induction Therapy and Risk-oriented Postremission Strategy for Adult Acute Myelogenous Leukemia (AML)

NCT00495287 | Completed Phase 3 DMC

• 1 other identifier: NILG-AML 02/06
• Study Type: interventional
• Target: 573
• Locations: 1 country
• Sites: 17

Brief Summary

The study was set up to assess:

1. 1.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.
2. 2.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 Cluster of Differentiation 34 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.
3. 3.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.

Conditions

Acute Myelogenous Leukemia

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Remission induction (R1): Complete remission (CR) rate after cycle 1

  30 days after beginning chemotherapy.

• Remission consolidation (R2): Length of remission (DFS, disease-free survival)

  5 years

Secondary Outcomes (7)

• R1: CR with incomplete hematological recovery

  30 days after beginning chemotherapy

• R1:Complete cytogenetic remission

  30 days after beginning chemotherapy

• R1: Treatment-related death (TRD)

  2 months

• R2: Overall survival (OS)

  5 years

• Remission duration and cumulative incidence of relapse

  5 years

Study Arms (2)

A

ACTIVE COMPARATOR

Remission induction arm A is with conventional chemotherapy cycle ("ICE": idarubicin, standard-dose cytarabine, etoposide)

Drug: cytosine arabinoside

B

EXPERIMENTAL

Remission induction therapy with high-dose cytarabine sequential regimen (HD-Ara-C, idarubicin)

Drug: cytosine arabinoside

Interventions

cytosine arabinoside DRUG

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.

Also known as: Aracytin, Cytarabine, Cytosar

A; B

Eligibility Criteria

• Age: 16 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Northern Italy Leukemia Group: lead

Study Sites (17)

Dipartimento di Ematologia e Medicina Trasfusionale - Azienda Osp. Nazionale Santi Antonio e Biagio e Cesare Arrigo

Alessandria, AL, Italy

Location

USC Ematologia Azienda Papa Giovanni XXIII

Bergamo, BG, Italy

Location

Ospedale Spedali Civili di Brescia

Brescia, Brescia, Italy

Location

Ospedale Generale di Bolzano

Bolzano, Bz, Italy

Location

S.C. Ematologia - Azienda Ospedaliera S.Croce e Carle

Cuneo, CN, Italy

Location

Istituti Ospitalieri

Cremona, Cremona, Italy

Location

Ematologia - AOU Careggi

Florence, FI, Italy

Location

Istituto Clinico Humanitas

Rozzano, Milano, Italy

Location

Ematologia Centro TMO - Fondazione IRCSS Ospedale Maggiore

Milan, MI, Italy

Location

Ematologia e TMO - Ospedale San Raffaele

Milan, MI, Italy

Location

Istituto Nazionale Dei Tumori

Milan, MI, Italy

Location

Ematologia - TMO - Ospedale San Gerardo

Monza, MI, Italy

Location

A.O.U San Giovanni Battista-Divisione Ematologica dell'Università

Torino, TO, Italy

Location

Ematologia 2 - Osp. Molinette San Giovanni Battista

Torino, TO, Italy

Location

Ospedale Mauriziano

Torino, TO, Italy

Location

Ospedale di Circolo di Varese

Varese, Varese, Italy

Location

Ospedale dell'Angelo

Mestre, Venezia, Italy

Location

Related Publications (3)

• Caprioli C, Lussana F, Salmoiraghi S, Cavagna R, Buklijas K, Elidi L, Zanghi' P, Michelato A, Delaini F, Oldani E, Intermesoli T, Grassi A, Gianfaldoni G, Mannelli F, Ferrero D, Audisio E, Terruzzi E, De Paoli L, Cattaneo C, Borlenghi E, Cavattoni I, Tajana M, Scattolin AM, Mattei D, Corradini P, Campiotti L, Ciceri F, Bernardi M, Todisco E, Cortelezzi A, Falini B, Pavoni C, Bassan R, Spinelli O, Rambaldi A. Clinical significance of chromatin-spliceosome acute myeloid leukemia: a report from the Northern Italy Leukemia Group (NILG) randomized trial 02/06. Haematologica. 2021 Oct 1;106(10):2578-2587. doi: 10.3324/haematol.2020.252825.

  PMID: 32855275 DERIVED

• Gianfaldoni G, Mannelli F, Intermesoli T, Bencini S, Giupponi D, Farina G, Cutini I, Bonetti MI, Masciulli A, Audisio E, Ferrero D, Pavoni C, Scattolin AM, Bosi A, Rambaldi A, Bassan R. Early peripheral clearance of leukemia-associated immunophenotypes in AML: centralized analysis of a randomized trial. Blood Adv. 2020 Jan 28;4(2):301-311. doi: 10.1182/bloodadvances.2019000406.

  PMID: 31978214 DERIVED

• Bassan R, Intermesoli T, Masciulli A, Pavoni C, Boschini C, Gianfaldoni G, Marmont F, Cavattoni I, Mattei D, Terruzzi E, De Paoli L, Cattaneo C, Borlenghi E, Ciceri F, Bernardi M, Scattolin AM, Todisco E, Campiotti L, Corradini P, Cortelezzi A, Ferrero D, Zanghi P, Oldani E, Spinelli O, Audisio E, Cortelazzo S, Bosi A, Falini B, Pogliani EM, Rambaldi A. Randomized trial comparing standard vs sequential high-dose chemotherapy for inducing early CR in adult AML. Blood Adv. 2019 Apr 9;3(7):1103-1117. doi: 10.1182/bloodadvances.2018026625.

  PMID: 30948365 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Renato Bassan, MD

  Norther Italy Leukemia Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor

Study Record Dates

• First Submitted: July 2, 2007
• First Posted: July 3, 2007
• Study Start: November 1, 2006
• Primary Completion: July 1, 2015
• Study Completion: December 1, 2015
• Last Updated: March 31, 2016

Record last verified: 2016-03

Locations

IT (17)