A Risk-Oriented Therapeutic Strategy for Adult Acute Myelogenous Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00400673
Recruitment Status : Completed
First Posted : November 17, 2006
Last Update Posted : April 1, 2011
Information provided by:
Northern Italy Leukemia Group

Brief Summary:

The study was set up to assess:

  1. A two-step, increasing-intensity remission induction phase. A conventional chemotherapy course (ICE, plus G-CSF) was followed, in unresponsive patients, by sequential high-dose cytarabine (plus G-CSF), aiming to provide an early effective rescue to as many refractory cases as possible.
  2. A risk-oriented postremission consolidation phase. The objective was to adopt allogeneic stem cell transplantation (alloSCT) in high-risk (HR) cases, while standard-risk (SR) ones were consolidated with a multicycle high-dose cytarabine-containing program, which included the use of autologous stem cells plus G-CSF to limit drug-related toxicity and intercycle treatment delays.

Condition or disease Intervention/treatment Phase
Acute Myelogenous Leukemia Behavioral: Two-step remission induction and risk-oriented consolidation Phase 2

Detailed Description:

Adult AML is a difficult-to-treat illness because of both biological and therapeutic reasons.

As to the first point, many patients are aged >50 years and/or present with significant comorbidity and/or AML-related risk features (poor risk cytogenetics, prior myelodysplasia, secondary AML).

As to the second point, standard-type remission induction therapy is ineffective in 20% or more of the patients, whereas the application of the more effective postremission consolidation options (alloSCT, high-dose cytarabine courses) is often flawed by high-grade toxicity which can offset expected benefits, particularly in older age groups (>50-55 years), where therapy-related death rates are seen in 5%-10% of the cases (chemotherapy) or more (transplants).

Against this background an explorative study was developed in which:

  1. All patients aged 16-65 years were considered eligible (acute promyelocytic leukemia excluded), including those with an antecedent diagnosis of myelodysplasia/hematological disorder and/or secondary AML. Both age and disease subtype selection criteria are broader than in most studies on adult AML, adhering more closely to the reported epidemiology of the disease.
  2. Remission induction was attempted with a two-step regimen, consisting of conventional chemotherapy (ICE: idarubicin/cytarabine/etoposide +G-CSF) followed, only in the case of failure to respond, by a sequential high dose-cytarabine cycle (cytarabine 3 g/m2/bd on days 1,2,8,9; idarubicin on days 3 and 10; G-GSF; cytarabine dosing 2 g/m2 in patients aged >55 years). It was hoped that this choice would optimize salvage rates (hence overall response rates), by allowing more patients (and more fit, uncomplicated ones) to reach the salvage phase, compared to a policy where salvage is usually given after two failed induction courses.
  3. Remission consolidation was risk-oriented, the risk being defined through a mixed clinico-cytogenetic model. Thus all patients entering CR after one/two cycles were stratified as HR or SR according to what is reported below. Once defined the risk class, therapy consisted of an alloSCT for HR patients, and of 3 consecutive monthly cytarabine-based cycles (2 g/m2/bd on days 1-5; idarubicin on days 1,2) in SR patients, each cycle being followed by the reinfusion of a limited amount of autologous blood stem cells (1-2x10e6/kg CD34+ cells) and G-CSF. Blood stem cells were collected following an early consolidation cycle with intermediate-dose cytarabine plus G-CSF. HR patients unable/unfit to proceed to alloSCT were offered instead the SR-type multicycle cytarabine consolidation, whereas all patients unable to mobilize autologous stem cells were treated with one/two intermediate-dose cytarabine course(s).

HR: high-risk cytogenetics or intermediate-risk/normal cytogenetics with FLT3 mutation and/or any one or more additional clinical risk factor(s), i.e. total WBC >50x10e9/l, FAB subtype M0, M6 or M7, prior myelodysplasia or secondary AML,hepatosplenomegaly, late CR (cycle 2), or favorable cytogenetics with late CR (cycle 2).

SR: favorable cytogenetics (without associated high-risk abnormalities and in CR after cycle 1) or intermediate-risk/normal cytogenetics without FLT3 mutation and/or without any one additional clinical risk factor(s), i.e. total WBC >50x10e9/l, FAB subtype M0, M6 or M7, prior myelodysplasia or secondary AML,hepatosplenomegaly, late CR (cycle 2).

Study Type : Interventional
Actual Enrollment : 581 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Two-Step Remission Induction With Risk-Oriented Consolidation (High-Risk: Allogeneic Stem Cell Transplant; Standard-Risk: Multicycle High-Dose Cytarabine With Autologous Blood Stem Cell Support) for Adult Acute Myelogenous Leukemia
Study Start Date : May 2000
Actual Primary Completion Date : October 2007
Actual Study Completion Date : October 2007

Arm Intervention/treatment
Risk-oriented chemotherapy for remission induction (application of sequential high-dose cytarabine course to patients unresponsive to standard chemotherapy course 1) and postremission consiolidation(standard risk: blood stem cell supported high-dose cytarabine course [x3]; high risk: allogeneic SCT)
Behavioral: Two-step remission induction and risk-oriented consolidation

Primary Outcome Measures :
  1. Disease-free survival [ Time Frame: 5-years ]
    Percent of patients who are disease-free 5 years from start of therapy

Secondary Outcome Measures :
  1. Complete remission [ Time Frame: Two months ]
    Percent of patients who achieve complete remission within two months from start of therapy (i.e. after two chemotherapy cycles)

  2. Overall survival [ Time Frame: 5 years ]
    Percent of patients who are alive 5 years after diagnosis

  3. Cumulative incidence of relapse [ Time Frame: 5 years ]
    Percent of patients who suffer from leukemia relapse at 5 years from date of remission

  4. Toxicity [ Time Frame: 5 years ]
    Percent of patients who die of treatment-related complications (in different prognostic/treatment groups)until 5 years from start of therapy

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Ages Eligible for Study:   15 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • age 15-65 years,untreated AML (de novo, secondary, myelodysplasia-related, granulocytic sarcoma),untreated high-risk myelodysplasia (RAEB, RAEB-T), informed consent

Exclusion Criteria:

  • acute promyelocytic leukemia, comorbidity precluding intensive chemotherapy approaches

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00400673

USC Ematologia Ospedali Riuniti di Bergamo
Bergamo, BG, Italy, 24128
Divisione Ematologia Spedali Civili di Brescia
Brescia, BS, Italy, 25123
Divisione di Ematologia e TMO Ospedale San Maurizio
Bolzano, BZ, Italy, 39100
Ematologia Azienda Ospedaliera S. Croce e Carle
Cuneo, CN, Italy, 12100
Ematologia e TMO Ospedale San Raffaele
Milano, MI, Italy, 20132
Ematologia e TMO Istituto Nazionale dei Tumori
Milano, MI, Italy, 20133
Ematologia-TMO Ospedale San Gerardo
Monza, MI, Italy, 20052
Oncoematologia e TMO Dipartimento Oncologico
Palermo, PA, Italy, 90146
Ematologia 2 Ospedale San Giovanni Battista
Torino, TO, Italy, 10126
Medicina Interna I Ospedale di Circolo
Varese, VA, Italy, 21100
Divisione Ematologia Ospedale Umberto I Mestre
Mestre, VE, Italy, 30172
Dipartimento di Oncologia e di Ematologia Oncologica Regione Veneto ULSS n.13- Presidi Ospedalieri di Noale, Dolo, Mirano
Noale, VE, Italy, 30033
Sponsors and Collaborators
Northern Italy Leukemia Group
Principal Investigator: Renato Bassan, MD Ospedali Riuniti di Bergamo USC Ematologia

Responsible Party: Renato Bassan, MD, Northern Italy Leukemia Group, Ospedali Riuniti, Bergamo (Italy) Identifier: NCT00400673     History of Changes
Other Study ID Numbers: NILG-AML 01/00
First Posted: November 17, 2006    Key Record Dates
Last Update Posted: April 1, 2011
Last Verified: March 2011

Keywords provided by Northern Italy Leukemia Group:
Acute myelogenous leukemia
Adult patients
Cytogenetic risk class
Clinico-cytogenetic risk model
Risk-oriented therapy

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs