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Risk-adapted, MRD-directed Therapy for Young Adults With Newly Diagnosed Acute Myeloid Leukemia (AML1310)

2018年8月3日 更新者：Gruppo Italiano Malattie EMatologiche dell'Adulto

Risk-adapted, MRD-directed Therapy for Young Adults With Newly Diagnosed Acute Myeloid Leukemia. GIMEMA Protocol AML1310. EudraCT Number 2010-023809-36

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.

研究概览

地位

完全的

条件

干预/治疗

详细说明

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.

研究类型

介入性

注册 (预期的)

515

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 意大利
      • Alessandria、意大利
        • S.O.C. di Ematologia - Azienda Ospedaliera - SS. Antonio e Biagio e Cesare Arrigo
      • Ancona、意大利
        • Azienda Ospedaliera - Nuovo Ospedale "Torrette"
      • Avellino、意大利
        • Az. Ospedaliera S. G. Moscati
      • Bari、意大利、70010
        • Unità Operativa Ematologia 1 - Università degli Studi di Bari
      • Barletta、意大利
        • UOC Ematologia Ospedale " Monsignor Raffaele Dimiccoli"
      • Bologna、意大利
        • Ist.Ematologia e Oncologia Medica L.e A. Seragnoli
      • Brindisi、意大利
        • Divisione di Ematologia Ospedale A. Perrino
      • Cagliari、意大利
        • Servizio di Ematologia - CTMO - ASL 8 P.O. Binaghi
      • Caserta、意大利
        • Unità Operativa Complessa di Onco-Ematologia - A.O. S.Anna e S.Sebastiano
      • Catania、意大利
        • Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto"
      • Catanzaro、意大利、88100
        • Azienda Ospedaliera Pugliese Ciaccio
      • Civitanova、意大利
        • Marche U.O. di Medicina Interna - ASUR Marche 8 - Ospedale Civile
      • Cona、意大利
        • Azienda Ospedaliero Universitaria Arcispedale Sant'Anna Dipartimento di Scienze Mediche Sezione di Ematologia e Fisiopatologia dell'Emostasi
      • Cremona、意大利
        • Sezione di Ematologia C.T.M.O. Istituti Ospitalieri
      • Ferrara、意大利、44100
        • Sez.Ematologia e Dip. scienze Biomediche Arcispedale S. Anna
      • Foggia、意大利
        • Struttura Complessa di Ematologia Ospedali Riuniti Foggia - Azienda Ospedaliero-Universitaria
      • Genova、意大利
        • Clinica Ematologica - Università degli Studi
      • Latina、意大利
        • Divisione di Ematologia Ospedale "Santa Maria Goretti"
      • Lecce、意大利
        • ASL Le/1 P.O. Vito Fazzi - U.O. di Ematol
      • Meldola、意大利
        • Istituto Scientifico Romagnoli per lo Studio e la Cura dei Tumori- IRST
      • Messina、意大利
        • Azienda Ospedaliera Universitaria - Policlinico G. Martino Dipartimento di Medicina Interna - U.O. Messina
      • Messina、意大利
        • Divisione di Ematologia - Azienda Ospedaliera Ospedali Riuniti "Papardo Piemonte"
      • Milano、意大利
        • UO Centro Trapianti di Midollo - IRCCS Ospedale Maggiore Policlinico
      • Milano、意大利
        • Ospedale Niguarda " Ca Granda"
      • Modena、意大利
        • Centro Oncologico Modenese - Dipartimento di Oncoematologia
      • Napoli、意大利
        • Azienda Ospedaliera Universitaria - Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia
      • Nocera Inferiore、意大利
        • Pr. Alfonso Maria D'Arco
      • Novara、意大利
        • S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro
      • Orbassano、意大利、10043
        • Ospedale S. Luigi Gonzaga
      • Padova、意大利
        • Università degli Studi di Padova - Ematologia ed Immunologia Clinica
      • Palermo、意大利
        • Divisione di Ematologia con trapianto di midollo - A.U. Policlinico "Paolo Giaccone"
      • Palermo、意大利、90146
        • Ospedale Riuniti "Villa-Sofia-Cervello"
      • Parma、意大利
        • Cattedra di Ematologia CTMO Università degli Studi di Parma
      • Perugia、意大利
        • Sezione di Ematologia ed Immunologia Clinica - Ospedale S.Maria della Misericordia
      • Pesaro、意大利
        • Div. di Ematologia di Muraglia - CTMO Ospedale San Salvatore
      • Pescara、意大利、61100
        • Azienda ASL di Pescara
      • Piacenza、意大利
        • Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale di Piacenza
      • Pisa、意大利
        • Università di Pisa - Azienda Ospedaliera Pisana - Dipartimento di Oncologia, dei Trapianti e delle nuove Tecnologie in Medicina - Divisione di Ematologia
      • Potenza、意大利
        • Ematologia - Ospedale San Carlo
      • Ravenna、意大利、48100
        • Ospedale S.Maria delle Croci
      • Reggio Calabria、意大利
        • Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli"
      • Reggio Emilia、意大利
        • Unità Operativa Complessa di Ematologia - Arcispedale S. Maria Nuova
      • Rimini、意大利
        • Ospedale "Infermi"
      • Roma、意大利
        • Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia
      • Roma、意大利
        • Az. Ospedaliera "Sant' Andrea"-Università la Sapienza Seconda Facoltà di Medicina e Chirurgia
      • Roma、意大利
        • S.C. di Ematologia e Trapianti - I.F.O. Istituto Nazionale Tumori Regina Elena
      • Roma、意大利、00168
        • Università Cattolica del Sacro Cuore - Policlinico A. Gemelli
      • Roma、意大利、00128
        • Divisione Ematologia - Università Campus Bio-Medico
      • Rome、意大利
        • U.O.C. Ematologia - Ospedale S.Eugenio
      • Rome、意大利
        • Ospedale S. Camillo
      • Rozzano、意大利
        • Sezione di Ematologia Cancer Center Humanitas
      • San Giovanni Rotondo、意大利
        • Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza
      • Sassari、意大利
        • Serv. di Ematologia Ist. di Ematologia ed Endocrinologia
      • Siena、意大利
        • U.O.C. Ematologia e Trapianti - A.O. Senese - Policlinico " Le Scotte"
      • Taormina、意大利
        • UOC di Ematologia Generale P.O. S.Vincenzo
      • Taranto、意大利
        • U.O.C. di Ematolgia - A.O. " SS Annunziata" - P.O. S.G. Moscati
      • Treviso、意大利
        • Azienda U.L.S.S.9 - U.O. di Ematologia
      • Udine、意大利、33100
        • Policlinico Universitario - Clinica Ematologia
    • (le)
      • Tricase、(le)、意大利
        • U.O. di Ematologia - Azienda Ospedaliera - Pia Fondazione di Culto e di Religione Card. G.Panico
    • (rm)
      • Roma、(rm)、意大利、00184
        • Complesso Ospedaliero S. Giovanni Addolorata
      • Rome、(rm)、意大利、00133
        • Policlinico Di Tor Vergata

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 至 60年 (成人)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  • Signed written informed consent according to ICH/EU/GCP and national/local laws
  • Patients aged between 18 and 60 years
  • Patients previously untreated for their AML by other chemotherapeutic agents (with the exception of no more than 7 days hydroxyurea (HU)), radiotherapy or more than 7 days corticosteroids
  • Unequivocal diagnosis of untreated de novo AML according to WHO diagnostic criteria (at least 20% blasts in the bone marrow), with FAB classification other than M3 (acute promyelocytic leukemia), documented by bone marrow aspiration (or biopsy in case of dry tap) (not supervening after other myeloproliferative disease or myelodysplastic syndromes of more than 6 months duration)
  • WHO performance status 0-3
  • Adequate renal (serum creatinine < 2 x the institutional Upper Limit of Normal (ULN)) and liver (total serum bilirubin < 2 x ULN; serum ALT and AST ≤ 3 x ULN) function, unless considered due to organ leukemic involvement
  • Left Ventricular Ejection Fraction (LVEF) >50%, as determined by echocardiogram
  • Absence of severe concomitant neurological or psychiatric diseases and congestive heart failure or active uncontrolled infection
  • Absence of any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and the follow-up schedule.

Exclusion Criteria:

  • Patients aged less than 18 or more than 60 years
  • Patients already treated for their AML by other chemotherapeutic agents (with the exception of no more than 7 days HU), radiotherapy or more than 7 days corticosteroids
  • Acute promyelocytic leukaemia
  • Blast crisis of chronic myeloid leukaemia
  • AML supervening after other myeloproliferative disease
  • AML supervening after antecedent myelodysplastic syndromes of more than 6 months duration
  • Other progressive malignant diseases. However, secondary AML following previously cured malignancies may be included as well as secondary AML following previous exposure to alkylating agents or radiation for other reason
  • Inadequate renal or liver function (metabolic abnormalities > 3 times the normal upper limit)
  • Severe heart failure requiring diuretics
  • Ejection fraction < 50%
  • Uncontrolled infections
  • WHO performance status = 4
  • Severe concomitant neurological or psychiatric diseases
  • Patients who are pregnant or adults of reproductive potential not employing an effective method of birth control. Women of childbearing potential must have a negative serum pregnancy test within 48 hrs prior to administration of chemotherapy. Post-menopausal women must be amenorrhoeic for at least 12 months to be considered of non-childbearing potential. Male and female patients must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug.

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：不适用
  • 介入模型：单组作业
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：MRD-directed therapy
其他：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 MRD to establish the final risk assignment and treatment of younger (≤ 60 years) patients with 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.

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Treatment strategy in terms of Overall Survival (OS) at 24 months.
大体时间：24 months from study entry.
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.
24 months from study entry.

次要结果测量

结果测量
措施说明
大体时间
Estimation of Disease Free Survival (DFS) from Complete Response (CR) evaluation.
大体时间：At 24 months from study entry
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.
At 24 months from study entry
Estimation of Event Free Survival (EFS) from study entry.
大体时间：at 24 months from study entry
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.
at 24 months from study entry
Rate of patients in CR after induction therapy
大体时间：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
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
Toxicity according to Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
大体时间：From study entry to study completion (6 months therapy + 18 months follow-up)
From study entry to study completion (6 months therapy + 18 months follow-up)
Estimation of OS, EFS, DFS and Cumulative Incidence of Relapse (CIR) according to risk groups (Low, Intermediate, High)
大体时间：At 24 months from study entry
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.
At 24 months from study entry
Estimation of OS, EFS, DFS and CIR according to the Minimal Residual Disease (MRD) level at each evaluation step
大体时间：At 24 months from study entry
At 24 months from study entry
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.
大体时间：At 24 months from study entry
At 24 months from study entry
Quality of Life evaluation
大体时间：Before treatment starts, after induction, at one year after baseline evaluation.

QoL should be measured at three different time points:

  1. At Baseline (before treatment starts).
  2. 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).
  3. At one year after baseline evaluation.
Before treatment starts, after induction, at one year after baseline evaluation.

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Gruppo Italiano Malattie EMatologiche dell'Adulto

调查人员

  • 首席研究员：Adriano VENDITTI, Pr.、Policlinico Tor Vergata di Roma

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

有用的网址

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2012年1月1日

初级完成 (实际的)

2017年7月1日

研究完成 (实际的)

2018年7月10日

研究注册日期

首次提交

2011年10月12日

首先提交符合 QC 标准的

2011年10月14日

首次发布 (估计)

2011年10月17日

研究记录更新

最后更新发布 (实际的)

2018年8月6日

上次提交的符合 QC 标准的更新

2018年8月3日

最后验证

2018年8月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • AML1310

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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