Risk-adapted, MRD-directed Therapy for Young Adults With Newly Diagnosed Acute Myeloid Leukemia (AML1310)
The purpose of this study is to determine whether a risk-adapted, minimal-residual-disease directed therapy for young adults with newly diagnosed acute myeloid leukemia has positive results in terms of overall survival at 24 months.
Acute Myeloid Leukemia
Other: Risk-adapted, MRD-directed therapy
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Risk-adapted, MRD-directed Therapy for Young Adults With Newly Diagnosed Acute Myeloid Leukemia. GIMEMA Protocol AML1310. EudraCT Number 2010-023809-36|
- Treatment strategy in terms of Overall Survival (OS) at 24 months. [ Time Frame: 24 months from study entry. ] [ Designated as safety issue: No ]OS is defined as the time interval between the date of study entry and death for any cause; patients still alive will be censored at the time of the last follow-up.
- Estimation of Disease Free Survival (DFS) from Complete Response (CR) evaluation. [ Time Frame: At 24 months from study entry ] [ Designated as safety issue: No ]DFS is defined as the time interval between the evaluation of CR -after induction phase- and relapse or death in CR; patients still alive, in first CR, will be censored at the time of the last follow-up.
- Estimation of Event Free Survival (EFS) from study entry. [ Time Frame: at 24 months from study entry ] [ Designated as safety issue: No ]EFS is defined as the time interval between the date of study entry dose and failure during induction phase, relapse or death whichever comes first; patients still alive, in first CR, will be censored at the time of the last follow-up.
- Rate of patients in CR after induction therapy [ Time Frame: At 31 days from study entry if pts are in CR or at 69 days from study entry if pts are in PR after 1 induction cycle ] [ Designated as safety issue: No ]
- Toxicity according to Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: From study entry to study completion (6 months therapy + 18 months follow-up) ] [ Designated as safety issue: Yes ]
- Estimation of OS, EFS, DFS and Cumulative Incidence of Relapse (CIR) according to risk groups (Low, Intermediate, High) [ Time Frame: At 24 months from study entry ] [ Designated as safety issue: No ]CIR is calculated from the date of achievement of the CR -after induction phase-, using the cumulative incidence method, considering death in CR as a competing risk. Patients still alive, without relapse, will be censored at the time of the last follow-up.
- Estimation of OS, EFS, DFS and CIR according to the Minimal Residual Disease (MRD) level at each evaluation step [ Time Frame: At 24 months from study entry ] [ Designated as safety issue: No ]
- Rate of CR patients and estimation OS, EFS, DFS and CIR according to baseline characteristics such as age, performance status, white blood cell (WBC), morphology, cytogenetic and molecular features. [ Time Frame: At 24 months from study entry ] [ Designated as safety issue: No ]
- Quality of Life evaluation [ Time Frame: Before treatment starts, after induction, at one year after baseline evaluation. ] [ Designated as safety issue: No ]
QoL should be measured at three different time points:
- At Baseline (before treatment starts).
- At the end of Induction phase (after evaluation of response and before start of consolidation therapy for patients in CR or salvage therapy for patients not achieving a CR).
- At one year after baseline evaluation.
|Study Start Date:||January 2012|
|Estimated Study Completion Date:||July 2016|
|Estimated Primary Completion Date:||July 2016 (Final data collection date for primary outcome measure)|
Other: Risk-adapted, MRD-directed therapy
The general objective of this study is that of setting up a multicentre, risk-adapted study that relies on pre-treatment cytogenetic/genetic features and post-consolidation assessment of Minimal Residual Disease (MRD) to establish the final risk assignment and treatment of younger (≤ 60 years) patients with Acute Myeloid Leukemia (AML). Aim of this clinical trial is to verify whether the delivery of a post remission therapy whose intensity is risk-driven will improve the outcome in terms of both increased anti-leukemic efficacy and reduced therapy-related toxicity.
All patients will receive induction and consolidation chemotherapy according to the Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA) LAM99P protocol. After the first consolidation, patients belonging to the low-risk category (core binding factor positive AML without c-Kit mutations, NPM1 positive FLT3 negative AML) will receive autologous stem cell transplantation, patients with high-risk features (adverse-risk karyotype, FLT3-ITD mutations), will be assigned to allogeneic stem cell transplantation. Patients with FLT3-TKD mutations or c-Kit mutated core binding factor positive AML and those belonging to the intermediate-risk karyotype category will be stratified according to MRD by flow cytometry and will receive risk-adapted treatment (autologous vs. allogeneic stem cell transplantation). All patients who meet the criteria for high-risk definition will be offered the allogeneic transplantation option regardless of the availability of a Human Leukocyte Antigen (HLA) identical sibling. In fact, for those lacking a HLA identical sibling all the other sources of hematopoietic stem cells (matched unrelated donor from international registry, unrelated cord blood, family haploidentical donor) will be considered. Autologous or allogeneic stem cell transplantation will be performed within 3 months from the end of consolidation therapy.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01452646
|Contact: Paola Fazi, Dr.||firstname.lastname@example.org|
|Contact: Enrico Creaemail@example.com|
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|Principal Investigator:||Adriano VENDITTI, Pr.||Policlinico Tor Vergata di Roma|