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

3. august 2018 opdateret af: 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.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Forventet)

515

Fase

  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

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

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år til 60 år (Voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: MRD-directed therapy
Andet: 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.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Treatment strategy in terms of Overall Survival (OS) at 24 months.
Tidsramme: 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.

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Estimation of Disease Free Survival (DFS) from Complete Response (CR) evaluation.
Tidsramme: 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.
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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.
Tidsramme: At 24 months from study entry
At 24 months from study entry
Quality of Life evaluation
Tidsramme: 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.

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Gruppo Italiano Malattie EMatologiche dell'Adulto

Efterforskere

  • Ledende efterforsker: Adriano VENDITTI, Pr., Policlinico Tor Vergata di Roma

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Hjælpsomme links

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

1. januar 2012

Primær færdiggørelse (Faktiske)

1. juli 2017

Studieafslutning (Faktiske)

10. juli 2018

Datoer for studieregistrering

Først indsendt

12. oktober 2011

Først indsendt, der opfyldte QC-kriterier

14. oktober 2011

Først opslået (Skøn)

17. oktober 2011

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

6. august 2018

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

3. august 2018

Sidst verificeret

1. august 2018

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • AML1310

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

INGEN

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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