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

NCT ID: NCT01452646

Last Updated: 2018-08-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 515 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2018-07-10

Brief Summary

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.

Detailed Description

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.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MRD-directed therapy

Group Type: EXPERIMENTAL

Risk-adapted, MRD-directed therapy

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: OTHER

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gruppo Italiano Malattie EMatologiche dell'Adulto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Adriano VENDITTI, Pr.

Role: PRINCIPAL_INVESTIGATOR

Policlinico Tor Vergata di Roma

Locations

U.O. di Ematologia - Azienda Ospedaliera - Pia Fondazione di Culto e di Religione Card. G.Panico

Tricase, (LE), Italy

Complesso Ospedaliero S. Giovanni Addolorata

Roma, (RM), Italy

Policlinico di Tor Vergata

Rome, (RM), Italy

S.O.C. di Ematologia - Azienda Ospedaliera - SS. Antonio e Biagio e Cesare Arrigo

Alessandria, , Italy

Azienda Ospedaliera - Nuovo Ospedale "Torrette"

Ancona, , Italy

Az. Ospedaliera S. G. Moscati

Avellino, , Italy

Unità Operativa Ematologia 1 - Università degli Studi di Bari

Bari, , Italy

UOC Ematologia Ospedale " Monsignor Raffaele Dimiccoli"

Barletta, , Italy

Ist.Ematologia e Oncologia Medica L.e A. Seragnoli

Bologna, , Italy

Divisione di Ematologia Ospedale A. Perrino

Brindisi, , Italy

Servizio di Ematologia - CTMO - ASL 8 P.O. Binaghi

Cagliari, , Italy

Unità Operativa Complessa di Onco-Ematologia - A.O. S.Anna e S.Sebastiano

Caserta, , Italy

Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto"

Catania, , Italy

Azienda Ospedaliera Pugliese Ciaccio

Catanzaro, , Italy

Marche U.O. di Medicina Interna - ASUR Marche 8 - Ospedale Civile

Civitanova Alta, , Italy

Azienda Ospedaliero Universitaria Arcispedale Sant'Anna Dipartimento di Scienze Mediche Sezione di Ematologia e Fisiopatologia dell'Emostasi

Cona, , Italy

Sezione di Ematologia C.T.M.O. Istituti Ospitalieri

Cremona, , Italy

Sez.Ematologia e Dip. scienze Biomediche Arcispedale S. Anna

Ferrara, , Italy

Struttura Complessa di Ematologia Ospedali Riuniti Foggia - Azienda Ospedaliero-Universitaria

Foggia, , Italy

Clinica Ematologica - Università degli Studi

Genova, , Italy

Divisione di Ematologia Ospedale "Santa Maria Goretti"

Latina, , Italy

ASL Le/1 P.O. Vito Fazzi - U.O. di Ematol

Lecce, , Italy

Istituto Scientifico Romagnoli per lo Studio e la Cura dei Tumori- IRST

Meldola, , Italy

Azienda Ospedaliera Universitaria - Policlinico G. Martino Dipartimento di Medicina Interna - U.O. Messina

Messina, , Italy

Divisione di Ematologia - Azienda Ospedaliera Ospedali Riuniti "Papardo Piemonte"

Messina, , Italy

Ospedale Niguarda " Ca Granda"

Milan, , Italy

UO Centro Trapianti di Midollo - IRCCS Ospedale Maggiore Policlinico

Milan, , Italy

Centro Oncologico Modenese - Dipartimento di Oncoematologia

Modena, , Italy

Azienda Ospedaliera Universitaria - Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia

Napoli, , Italy

Pr. Alfonso Maria D'Arco

Nocera Inferiore, , Italy

S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro

Novara, , Italy

Ospedale S. Luigi Gonzaga

Orbassano, , Italy

Università degli Studi di Padova - Ematologia ed Immunologia Clinica

Padua, , Italy

Ospedale Riuniti "Villa-Sofia-Cervello"

Palermo, , Italy

Divisione di Ematologia con trapianto di midollo - A.U. Policlinico "Paolo Giaccone"

Palermo, , Italy

Cattedra di Ematologia CTMO Università degli Studi di Parma

Parma, , Italy

Sezione di Ematologia ed Immunologia Clinica - Ospedale S.Maria della MIsericordia

Perugia, , Italy

Div. di Ematologia di Muraglia - CTMO Ospedale San Salvatore

Pesaro, , Italy

Azienda ASL di Pescara

Pescara, , Italy

Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale di Piacenza

Piacenza, , Italy

Università di Pisa - Azienda Ospedaliera Pisana - Dipartimento di Oncologia, dei Trapianti e delle nuove Tecnologie in Medicina - Divisione di Ematologia

Pisa, , Italy

Ematologia - Ospedale San Carlo

Potenza, , Italy

Ospedale S.Maria delle Croci

Ravenna, , Italy

Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli"

Reggio Calabria, , Italy

Unità Operativa Complessa di Ematologia - Arcispedale S. Maria Nuova

Reggio Emilia, , Italy

Ospedale "Infermi"

Rimini, , Italy

Divisione Ematologia - Università Campus Bio-Medico

Roma, , Italy

Università Cattolica del Sacro Cuore - Policlinico A. Gemelli

Roma, , Italy

Az. Ospedaliera "Sant' Andrea"-Università la Sapienza Seconda Facoltà di Medicina e Chirurgia

Roma, , Italy

S.C. di Ematologia e Trapianti - I.F.O. Istituto Nazionale Tumori Regina Elena

Roma, , Italy

Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia

Roma, , Italy

Ospedale S. Camillo

Rome, , Italy

U.O.C. Ematologia - Ospedale S.Eugenio

Rome, , Italy

Sezione di Ematologia Cancer Center Humanitas

Rozzano, , Italy

Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, , Italy

Serv. di Ematologia Ist. di Ematologia ed Endocrinologia

Sassari, , Italy

U.O.C. Ematologia e Trapianti - A.O. Senese - Policlinico " Le Scotte"

Siena, , Italy

UOC di Ematologia Generale P.O. S.Vincenzo

Taormina, , Italy

U.O.C. di Ematolgia - A.O. " SS Annunziata" - P.O. S.G. Moscati

Taranto, , Italy

Azienda U.L.S.S.9 - U.O. di Ematologia

Treviso, , Italy

Policlinico Universitario - Clinica Ematologia

Udine, , Italy

Countries

Italy

References

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.

Reference Type: DERIVED

PMID: 34731884 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31395600 (View on PubMed)

Related Links

http://www.gimema.it/en/index.php

GIMEMA Foundation Website

Other Identifiers

AML1310

Identifier Type: -

Identifier Source: org_study_id