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

NCT01452646 | Completed Phase 2

• 1 other identifier: AML1310
• Study Type: interventional
• Target: 515
• Locations: 1 country
• Sites: 61

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.

Conditions

Acute Myeloid Leukemia

Keywords

acute myeloid leukemia; risk-adapted therapy; MRD-directed therapy; young adults

Outcome Measures

Primary Outcomes (1)

• Treatment strategy in terms of Overall Survival (OS) at 24 months.

  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.

Secondary Outcomes (8)

• Estimation of Disease Free Survival (DFS) from Complete Response (CR) evaluation.

  At 24 months from study entry

• Estimation of Event Free Survival (EFS) from study entry.

  at 24 months from study entry

• Rate of patients in CR after induction therapy

  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

  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)

  At 24 months from study entry

Study Arms (1)

MRD-directed therapy

EXPERIMENTAL

Other: Risk-adapted, MRD-directed therapy

Interventions

Risk-adapted, MRD-directed therapy 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.

MRD-directed therapy

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gruppo Italiano Malattie EMatologiche dell'Adulto: lead

Study Sites (61)

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

Tricase, (LE), Italy

Location

Complesso Ospedaliero S. Giovanni Addolorata

Roma, (RM), 00184, Italy

Location

Policlinico di Tor Vergata

Rome, (RM), 00133, Italy

Location

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

Alessandria, Italy

Location

Azienda Ospedaliera - Nuovo Ospedale "Torrette"

Ancona, Italy

Location

Az. Ospedaliera S. G. Moscati

Avellino, Italy

Location

Unità Operativa Ematologia 1 - Università degli Studi di Bari

Bari, 70010, Italy

Location

UOC Ematologia Ospedale " Monsignor Raffaele Dimiccoli"

Barletta, Italy

Location

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

Bologna, Italy

Location

Divisione di Ematologia Ospedale A. Perrino

Brindisi, Italy

Location

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

Cagliari, Italy

Location

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

Caserta, Italy

Location

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

Catania, Italy

Location

Azienda Ospedaliera Pugliese Ciaccio

Catanzaro, 88100, Italy

Location

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

Civitanova Alta, Italy

Location

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

Cona, Italy

Location

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

Cremona, Italy

Location

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

Ferrara, 44100, Italy

Location

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

Foggia, Italy

Location

Clinica Ematologica - Università degli Studi

Genova, Italy

Location

Divisione di Ematologia Ospedale "Santa Maria Goretti"

Latina, Italy

Location

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

Lecce, Italy

Location

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

Meldola, Italy

Location

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

Messina, Italy

Location

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

Messina, Italy

Location

Ospedale Niguarda " Ca Granda"

Milan, Italy

Location

UO Centro Trapianti di Midollo - IRCCS Ospedale Maggiore Policlinico

Milan, Italy

Location

Centro Oncologico Modenese - Dipartimento di Oncoematologia

Modena, Italy

Location

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

Napoli, Italy

Location

Pr. Alfonso Maria D'Arco

Nocera Inferiore, Italy

Location

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

Novara, Italy

Location

Ospedale S. Luigi Gonzaga

Orbassano, 10043, Italy

Location

Università degli Studi di Padova - Ematologia ed Immunologia Clinica

Padua, Italy

Location

Ospedale Riuniti "Villa-Sofia-Cervello"

Palermo, 90146, Italy

Location

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

Palermo, Italy

Location

Cattedra di Ematologia CTMO Università degli Studi di Parma

Parma, Italy

Location

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

Perugia, Italy

Location

Div. di Ematologia di Muraglia - CTMO Ospedale San Salvatore

Pesaro, Italy

Location

Azienda ASL di Pescara

Pescara, 61100, Italy

Location

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

Piacenza, Italy

Location

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

Pisa, Italy

Location

Ematologia - Ospedale San Carlo

Potenza, Italy

Location

Ospedale S.Maria delle Croci

Ravenna, 48100, Italy

Location

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

Reggio Calabria, Italy

Location

Unità Operativa Complessa di Ematologia - Arcispedale S. Maria Nuova

Reggio Emilia, Italy

Location

Ospedale "Infermi"

Rimini, Italy

Location

Divisione Ematologia - Università Campus Bio-Medico

Roma, 00128, Italy

Location

Università Cattolica del Sacro Cuore - Policlinico A. Gemelli

Roma, 00168, Italy

Location

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

Roma, Italy

Location

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

Roma, Italy

Location

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

Roma, Italy

Location

Ospedale S. Camillo

Rome, Italy

Location

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

Rome, Italy

Location

Sezione di Ematologia Cancer Center Humanitas

Rozzano, Italy

Location

Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, Italy

Location

Serv. di Ematologia Ist. di Ematologia ed Endocrinologia

Sassari, Italy

Location

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

Siena, Italy

Location

UOC di Ematologia Generale P.O. S.Vincenzo

Taormina, Italy

Location

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

Taranto, Italy

Location

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

Treviso, Italy

Location

Policlinico Universitario - Clinica Ematologia

Udine, 33100, Italy

Location

Related Publications (2)

• 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.

  PMID: 34731884 DERIVED

• 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.

  PMID: 31395600 DERIVED

Related Links

• GIMEMA Foundation Website

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Adriano VENDITTI, Pr.

  Policlinico Tor Vergata di Roma

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2011
• First Posted: October 17, 2011
• Study Start: January 1, 2012
• Primary Completion: July 1, 2017
• Study Completion: July 10, 2018
• Last Updated: August 6, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (61)