A Risk-Oriented Therapeutic Strategy for Adult Acute Myelogenous Leukemia

This study has been completed.
Sponsor:
Information provided by:
Northern Italy Leukemia Group
ClinicalTrials.gov Identifier:
NCT00400673
First received: November 16, 2006
Last updated: March 31, 2011
Last verified: March 2011

November 16, 2006
March 31, 2011
May 2000
October 2007   (final data collection date for primary outcome measure)
Disease-free survival [ Time Frame: 5-years ] [ Designated as safety issue: No ]
Percent of patients who are disease-free 5 years from start of therapy
Disease-free survival at 5 years
Complete list of historical versions of study NCT00400673 on ClinicalTrials.gov Archive Site
  • Complete remission [ Time Frame: Two months ] [ Designated as safety issue: No ]
    Percent of patients who achieve complete remission within two months from start of therapy (i.e. after two chemotherapy cycles)
  • Overall survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Percent of patients who are alive 5 years after diagnosis
  • Cumulative incidence of relapse [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Percent of patients who suffer from leukemia relapse at 5 years from date of remission
  • Toxicity [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    Percent of patients who die of treatment-related complications (in different prognostic/treatment groups)until 5 years from start of therapy
  • Complete remission
  • Overall survival
  • Cumulative incidence of relapse
  • Toxicity
Not Provided
Not Provided
 
A Risk-Oriented Therapeutic Strategy for Adult Acute Myelogenous Leukemia
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

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.

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).

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Acute Myelogenous Leukemia
Behavioral: Two-step remission induction and risk-oriented consolidation
Chemotherapy
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)
Intervention: Behavioral: Two-step remission induction and risk-oriented consolidation
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
581
October 2007
October 2007   (final data collection date for primary outcome measure)

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
Both
15 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
Italy
 
NCT00400673
NILG-AML 01/00
No
Renato Bassan, MD, Northern Italy Leukemia Group, Ospedali Riuniti, Bergamo (Italy)
Northern Italy Leukemia Group
Not Provided
Principal Investigator: Renato Bassan, MD Ospedali Riuniti di Bergamo USC Ematologia
Northern Italy Leukemia Group
March 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP