- ICH GCP
- Реестр клинических исследований США
- Клиническое испытание NCT01452646
Risk-adapted, MRD-directed Therapy for Young Adults With Newly Diagnosed Acute Myeloid Leukemia (AML1310)
Risk-adapted, MRD-directed Therapy for Young Adults With Newly Diagnosed Acute Myeloid Leukemia. GIMEMA Protocol AML1310. EudraCT Number 2010-023809-36
Обзор исследования
Статус
Условия
Вмешательство/лечение
Подробное описание
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.
Тип исследования
Регистрация (Ожидаемый)
Фаза
- Фаза 2
Контакты и местонахождение
Места учебы
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Alessandria, Италия
- S.O.C. di Ematologia - Azienda Ospedaliera - SS. Antonio e Biagio e Cesare Arrigo
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Ancona, Италия
- Azienda Ospedaliera - Nuovo Ospedale "Torrette"
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Avellino, Италия
- Az. Ospedaliera S. G. Moscati
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Bari, Италия, 70010
- Unità Operativa Ematologia 1 - Università degli Studi di Bari
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Barletta, Италия
- UOC Ematologia Ospedale " Monsignor Raffaele Dimiccoli"
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Bologna, Италия
- Ist.Ematologia e Oncologia Medica L.e A. Seragnoli
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Brindisi, Италия
- Divisione di Ematologia Ospedale A. Perrino
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Cagliari, Италия
- Servizio di Ematologia - CTMO - ASL 8 P.O. Binaghi
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Caserta, Италия
- Unità Operativa Complessa di Onco-Ematologia - A.O. S.Anna e S.Sebastiano
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Catania, Италия
- Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto"
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Catanzaro, Италия, 88100
- Azienda Ospedaliera Pugliese Ciaccio
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Civitanova, Италия
- Marche U.O. di Medicina Interna - ASUR Marche 8 - Ospedale Civile
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Cona, Италия
- Azienda Ospedaliero Universitaria Arcispedale Sant'Anna Dipartimento di Scienze Mediche Sezione di Ematologia e Fisiopatologia dell'Emostasi
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Cremona, Италия
- Sezione di Ematologia C.T.M.O. Istituti Ospitalieri
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Ferrara, Италия, 44100
- Sez.Ematologia e Dip. scienze Biomediche Arcispedale S. Anna
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Foggia, Италия
- Struttura Complessa di Ematologia Ospedali Riuniti Foggia - Azienda Ospedaliero-Universitaria
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Genova, Италия
- Clinica Ematologica - Università degli Studi
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Latina, Италия
- Divisione di Ematologia Ospedale "Santa Maria Goretti"
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Lecce, Италия
- ASL Le/1 P.O. Vito Fazzi - U.O. di Ematol
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Meldola, Италия
- Istituto Scientifico Romagnoli per lo Studio e la Cura dei Tumori- IRST
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Messina, Италия
- Azienda Ospedaliera Universitaria - Policlinico G. Martino Dipartimento di Medicina Interna - U.O. Messina
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Messina, Италия
- Divisione di Ematologia - Azienda Ospedaliera Ospedali Riuniti "Papardo Piemonte"
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Milano, Италия
- UO Centro Trapianti di Midollo - IRCCS Ospedale Maggiore Policlinico
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Milano, Италия
- Ospedale Niguarda " Ca Granda"
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Modena, Италия
- Centro Oncologico Modenese - Dipartimento di Oncoematologia
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Napoli, Италия
- Azienda Ospedaliera Universitaria - Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia
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Nocera Inferiore, Италия
- Pr. Alfonso Maria D'Arco
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Novara, Италия
- S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro
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Orbassano, Италия, 10043
- Ospedale S. Luigi Gonzaga
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Padova, Италия
- Università degli Studi di Padova - Ematologia ed Immunologia Clinica
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Palermo, Италия
- Divisione di Ematologia con trapianto di midollo - A.U. Policlinico "Paolo Giaccone"
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Palermo, Италия, 90146
- Ospedale Riuniti "Villa-Sofia-Cervello"
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Parma, Италия
- Cattedra di Ematologia CTMO Università degli Studi di Parma
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Perugia, Италия
- Sezione di Ematologia ed Immunologia Clinica - Ospedale S.Maria della Misericordia
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Pesaro, Италия
- Div. di Ematologia di Muraglia - CTMO Ospedale San Salvatore
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Pescara, Италия, 61100
- Azienda ASL di Pescara
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Piacenza, Италия
- Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale di Piacenza
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Pisa, Италия
- Università di Pisa - Azienda Ospedaliera Pisana - Dipartimento di Oncologia, dei Trapianti e delle nuove Tecnologie in Medicina - Divisione di Ematologia
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Potenza, Италия
- Ematologia - Ospedale San Carlo
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Ravenna, Италия, 48100
- Ospedale S.Maria delle Croci
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Reggio Calabria, Италия
- Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli"
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Reggio Emilia, Италия
- Unità Operativa Complessa di Ematologia - Arcispedale S. Maria Nuova
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Rimini, Италия
- Ospedale "Infermi"
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Roma, Италия
- Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia
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Roma, Италия
- Az. Ospedaliera "Sant' Andrea"-Università la Sapienza Seconda Facoltà di Medicina e Chirurgia
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Roma, Италия
- S.C. di Ematologia e Trapianti - I.F.O. Istituto Nazionale Tumori Regina Elena
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Roma, Италия, 00168
- Università Cattolica del Sacro Cuore - Policlinico A. Gemelli
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Roma, Италия, 00128
- Divisione Ematologia - Università Campus Bio-Medico
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Rome, Италия
- U.O.C. Ematologia - Ospedale S.Eugenio
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Rome, Италия
- Ospedale S. Camillo
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Rozzano, Италия
- Sezione di Ematologia Cancer Center Humanitas
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San Giovanni Rotondo, Италия
- Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza
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Sassari, Италия
- Serv. di Ematologia Ist. di Ematologia ed Endocrinologia
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Siena, Италия
- U.O.C. Ematologia e Trapianti - A.O. Senese - Policlinico " Le Scotte"
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Taormina, Италия
- UOC di Ematologia Generale P.O. S.Vincenzo
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Taranto, Италия
- U.O.C. di Ematolgia - A.O. " SS Annunziata" - P.O. S.G. Moscati
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Treviso, Италия
- Azienda U.L.S.S.9 - U.O. di Ematologia
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Udine, Италия, 33100
- Policlinico Universitario - Clinica Ematologia
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(le)
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Tricase, (le), Италия
- U.O. di Ematologia - Azienda Ospedaliera - Pia Fondazione di Culto e di Religione Card. G.Panico
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(rm)
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Roma, (rm), Италия, 00184
- Complesso Ospedaliero S. Giovanni Addolorata
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Rome, (rm), Италия, 00133
- Policlinico di Tor Vergata
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Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
Принимает здоровых добровольцев
Полы, имеющие право на обучение
Описание
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.
Учебный план
Как устроено исследование?
Детали дизайна
- Основная цель: Уход
- Распределение: Н/Д
- Интервенционная модель: Одногрупповое задание
- Маскировка: Нет (открытая этикетка)
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
---|---|
Экспериментальный: 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.
|
Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
---|---|---|
Treatment strategy in terms of Overall Survival (OS) at 24 months.
Временное ограничение: 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.
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24 months from study entry.
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Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
---|---|---|
Estimation of Disease Free Survival (DFS) from Complete Response (CR) evaluation.
Временное ограничение: 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.
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At 24 months from study entry
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Estimation of Event Free Survival (EFS) from study entry.
Временное ограничение: 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.
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at 24 months from study entry
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Rate of patients in CR after induction therapy
Временное ограничение: 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
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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
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Toxicity according to Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
Временное ограничение: From study entry to study completion (6 months therapy + 18 months follow-up)
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From study entry to study completion (6 months therapy + 18 months follow-up)
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Estimation of OS, EFS, DFS and Cumulative Incidence of Relapse (CIR) according to risk groups (Low, Intermediate, High)
Временное ограничение: At 24 months from study entry
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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.
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At 24 months from study entry
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Estimation of OS, EFS, DFS and CIR according to the Minimal Residual Disease (MRD) level at each evaluation step
Временное ограничение: At 24 months from study entry
|
At 24 months from study entry
|
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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.
Временное ограничение: At 24 months from study entry
|
At 24 months from study entry
|
|
Quality of Life evaluation
Временное ограничение: Before treatment starts, after induction, at one year after baseline evaluation.
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QoL should be measured at three different time points:
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Before treatment starts, after induction, at one year after baseline evaluation.
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Соавторы и исследователи
Следователи
- Главный следователь: Adriano VENDITTI, Pr., Policlinico Tor Vergata di Roma
Публикации и полезные ссылки
Общие публикации
- Buccisano F, Palmieri R, Piciocchi A, Arena V, Candoni A, Melillo L, Calafiore V, Cairoli R, de Fabritiis P, Storti G, Salutari P, Lanza F, Martinelli G, Luppi M, Capria S, Maurillo L, Del Principe MI, Paterno G, Irno Consalvo MA, Ottone T, Lavorgna S, Voso MT, Fazi P, Vignetti M, Arcese W, Venditti A. ELN2017 risk stratification improves outcome prediction when applied to the prospective GIMEMA AML1310 protocol. Blood Adv. 2022 Apr 26;6(8):2510-2516. doi: 10.1182/bloodadvances.2021005717.
- Venditti A, Piciocchi A, Candoni A, Melillo L, Calafiore V, Cairoli R, de Fabritiis P, Storti G, Salutari P, Lanza F, Martinelli G, Luppi M, Mazza P, Martelli MP, Cuneo A, Albano F, Fabbiano F, Tafuri A, Chierichini A, Tieghi A, Fracchiolla NS, Capelli D, Foa R, Alati C, La Sala E, Fazi P, Vignetti M, Maurillo L, Buccisano F, Del Principe MI, Irno-Consalvo M, Ottone T, Lavorgna S, Voso MT, Lo-Coco F, Arcese W, Amadori S. GIMEMA AML1310 trial of risk-adapted, MRD-directed therapy for young adults with newly diagnosed acute myeloid leukemia. Blood. 2019 Sep 19;134(12):935-945. doi: 10.1182/blood.2018886960. Epub 2019 Aug 8.
Полезные ссылки
Даты записи исследования
Изучение основных дат
Начало исследования (Действительный)
Первичное завершение (Действительный)
Завершение исследования (Действительный)
Даты регистрации исследования
Первый отправленный
Впервые представлено, что соответствует критериям контроля качества
Первый опубликованный (Оценивать)
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
Последнее отправленное обновление, отвечающее критериям контроля качества
Последняя проверка
Дополнительная информация
Термины, связанные с этим исследованием
Дополнительные соответствующие термины MeSH
Другие идентификационные номера исследования
- AML1310
Планирование данных отдельных участников (IPD)
Планируете делиться данными об отдельных участниках (IPD)?
Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .