Phase III Trial in Acute Promyelocytic Leukemia Patients
APL0406
A Randomised Phase III Study to Compare Arsenic Trioxide (ATO) Combined to ATRA Versus Standard ATRA and Anthracycline-Based Chemotherapy (AIDA Regimen) for Newly Diagnosed, Non High-Risk Acute Promyelocytic Leukemia
3 other identifiers
interventional
276
3 countries
110
Brief Summary
Open label, randomised, phase III multicenter trial.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3 leukemia
Started Aug 2007
Longer than P75 for phase_3 leukemia
110 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 4, 2007
CompletedFirst Posted
Study publicly available on registry
June 5, 2007
CompletedStudy Start
First participant enrolled
August 1, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
October 17, 2019
CompletedOctober 12, 2022
October 1, 2022
5.1 years
June 4, 2007
October 10, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Event-free survival
As of 14th september 2010, all patients needed to evaluate the primary endpoint have been recruited.
At maximum 3.5 years from study entry
Secondary Outcomes (10)
Rate of hematological complete remission
At maximum 60 days from induction therapy start
Overall survival rate
At 2 years from study entry
Rate of cumulative incidence of relapse
At 2 years from study entry
Incidence of hematological and non-hematological toxicity episodes during treatment as assessed by CTC-NCI
At maximum 60 days from induction therapy start and at maximum 225 days from consolidation therapy start
Rate of molecular remission after 3rd consolidation course
At maximum 225 days grom consolidation therapy start
- +5 more secondary outcomes
Study Arms (2)
ARM A - ATO/ATRA
EXPERIMENTALARM B - ATRA
ACTIVE COMPARATORInterventions
Induction Arsenic Trioxide (As2O3=ATO), 0.15 mg/Kg IV over 2 hours daily starting on day 1. ATO will be continued until hematological CR or for a maximum of 60 days. Consolidation ATO, 0.15 mg/Kg IV over 2 hours daily for 5 days every week. Treatment will be continued for 4 weeks on and 4 weeks off, for a total of 4 cycles (last cycle administered on weeks 25 - 28).
Induction Idarubicin, 12 mg/m² on days 2, 4, 6 and 8 by short (20') intravenous infusion . If no hematological CR is achieved by 60 days after start of induction, patient will go off-study. Consolidation 1st cycle Idarubicin, 5 mg/m2/day by short (20') intravenous infusion on days 1, 2, 3, 4. 3rd cycle Idarubicin, 12 mg/m2/day as short (20') intravenous infusion only on day 1.
Maintenance therapy 6-Mercaptopurine (6-MP), 50 mg/m2/day orally. The dose will be adjusted according to hematopoietic toxicity during the follow-up period
Maintenance therapy Methotrexate (MTX), 15 mg/m2/weekly intramuscularly. The dose will be adjusted according to toxicity during the follow-up period.
Induction ATRA, 45 mg/m²/day will be administered orally in two equally divided doses and rounded to the nearest 10 mg increment, starting on day 1. ATRA treatment will be continued until hematological CR and for a maximum of 60 days. Consolidation 1. st cycle ATRA, 45 mg/m2/day, will be administered orally in two equally divided doses and rounded to the nearest 10 mg increment, starting from day 1 to day 15. 2. nd cycle ATRA, 45 mg/m2/day will be administered orally in two equally divided doses and rounded to the nearest 10 mg increment, starting from day 1 to day 15. 3. rd cycle ATRA, 45 mg/m2/day will be administered orally in two equally divided doses and rounded to the nearest 10 mg increment, starting from day 1 to day 15. Maintenance therapy ATRA, 45 mg/m2/day orally, for 15 days every three months until a two year period is completed.
Induction All-trans retinoic acid (ATRA), 45 mg/m²/day will be administered orally in two equally divided doses and rounded to the nearest 10 mg increment, starting on day 1. ATRA treatment will be continued until hematological complete remission (CR, see below for definition) or for a maximum of 60 days. Consolidation ATRA, 45 mg/m²/day will be administered orally in two equally divided doses and rounded to the nearest 10 mg increment. Treatment will be administered for 2 weeks on 2 weeks off and for a total of 7 cycles (last cycle administered on weeks 25 - 26).
Eligibility Criteria
You may qualify if:
- Signed written informed consent according to IGH/EU/GCP and national local laws
- Newly diagnosed APL by cytomorphology, confirmed also by molecular analysis\*.
- Age ≤18 \< 71 years
- WHO performance status 0 -2 included
- WBC at diagnosis ≤ 10 x 109/L
- Serum total bilirubin ≤ 3.0 mg/dL (≤ 51µmol/L)
- Serum creatinine ≤ 3.0 mg/dL (≤ 260 µmol/L)
- The confirmation of diagnosis at genetic level (microspeckled PML nuclear distribution by PGM3 monoclonal antibody and/or PML/RARa fusion by RT-PCR and/or demonstration of t(15;17) by karyotyping) will be mandatory for patient eligibility. However, in order to avoid delay in treatment initiation, patients can be randomised on the basis of morphologic diagnosis only and before the results of genetic tests are available.
You may not qualify if:
- Age \< 18 and ≥ 71
- WBC at diagnosis \> 10 x 109/L
- Other active malignancy at time of study entry
- Lack of diagnostic confirmation at genetic level
- Significant arrhythmias, EKG abnormalities (\*see below) or neuropathy
- Other cardiac contraindications for intensive chemotherapy (L-VEF \<50%)
- Uncontrolled, life-threatening infections
- Severe non-controlled pulmonary or cardiac disease
- Women who are either pregnant or breast feeding, or of child-bearing potential, defined as all women physiologically capable of becoming pregnant, UNLESS they meet one of the following definitions:
- Amenorrhea;
- post surgical bilateral oophorectomy with or without hysterectomy;
- using a highly effective method of birth control (defined as those which result in a failure rate less than 1% per year) when used consistently and correctly such as implants, injectables, oral contraceptives, IUDs, sexual abstinence or vasectomized partner.
- Concomitant severe psychiatric disorder
- HIV positivity
- \*EKG abnormalities:
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (110)
Universitätsklinik Innsbruck Hämatologie Onkologie
Innsbruck, Austria
Krankenhaus der Barmherzigen Schwestern Linz
Linz, Austria
Universitätsklinik für Innere Medizin III Salzburg
Salzburg, Austria
Klinikum Bayreuth GmbH
Bayreuth, Germany
Charité Campus Benjamin Franklin Berlin
Berlin, Germany
Städt. Kliniken Bielefeld gem. GmbH
Bielefeld, Germany
Universitätsklinikum Bonn
Bonn, Germany
Ev. Diakonie-Krankenhaus gGmbH Bremen
Bremen, Germany
Klinikum Bremen-Mitte gGmbH
Bremen, Germany
Klinikum Chemnitz gGmbH
Chemnitz, Germany
Universitätsklinikum C. G. Carus Dresden
Dresden, Germany
Katholisches Klinikum Duisburg St. Johannes Hospital
Duisburg, Germany
Universitätsklinikum Düsseldorf
Düsseldorf, Germany
Uniklinikum Erlangen
Erlangen, Germany
Kliniken Essen Süd, Ev. Krankenhaus Essen-Werden gGmbH
Essen, Germany
Universitätsklinikum Essen
Essen, Germany
Uniklinik Frankfurt/Main
Frankfurt am Main, Germany
Städtische Kliniken Frankfurt a. M.-Höchst
Frankfurt/a. M. -Höchst, Germany
Universitätsklinikum Freiburg
Freiburg im Breisgau, Germany
Klinikum Fulda
Fulda, Germany
Universitätsklinikum Gießen und Marburg Gießen
Giessen, Germany
Universitätsklinikum Göttingen
Göttingen, Germany
Asklepios Klinik Hamburg Altona
Hamburg, Germany
Asklepios Klinik St. Georg Hamburg
Hamburg, Germany
Universitätsklinikum Hamburg Eppendorf
Hamburg, Germany
St. Marien-Hospital gem. GmbH Hamm
Hamm, Germany
Medizinische Hochschule Hannover
Hanover, Germany
Universitätsklinikum Heidelberg
Heidelberg, Germany
St. Bernward Krankenhaus Hildesheim
Hildesheim, Germany
Universitätsklinikum des Saarlandes Homburg/Saar
Homburg, Germany
Klinik für Knochenmarktransplantation und Hämatologie Idar-Oberstein
Idar-Oberstein, Germany
Westpfalz-Klinikum GmbH Kaiserslautern
Kaiserslautern, Germany
Caritas-Krankenhaus Lebach
Lebach, Germany
Klinikum Lippe Lemgo
Lippe, Germany
Uniklinikum Lübeck
Lübeck, Germany
Klinikum der Johannes Gutenberg Universität Mainz
Mainz, Germany
Universitätsklinikum Gießen und Marburg GmbH Marburg
Marburg, Germany
Carl-von-Basedow-Klinikum Merseburg
Merseburg, Germany
Johannes Wesling Klinikum Minden
Minden, Germany
Klinikum rechts der Isar (München)
München, Germany
Klinikum Nord Nürnberg
Nuremberg, Germany
Klinikum Passau
Passau, Germany
Universitätsklinikum Regensburg
Regensburg, Germany
Caritas-Klinik St. Theresia Saarbrücken
Saarbrücken, Germany
Diakonie-Krankenhaus Schwäbisch Hall
Schwäbisch Hall, Germany
Diakonie-Klinikum Stuttgart
Stuttgart, Germany
Klinikum Stuttgart Bürgerhospital
Stuttgart, Germany
Robert Bosch Krankenhaus Stuttgart
Stuttgart, Germany
Krankenanstalt Mutterhaus der Borromäerinnen Trier
Trier, Germany
Krankenhaus der Barmherzigen Brüder Trier
Trier, Germany
Universitätsklinikum Tübingen
Tübingen, Germany
Universitätsklinikum Ulm
Ulm, Germany
Klinikum Villingen-Schwenningen
Villingen-Schwenningen, Germany
HELIOS Klinikum Wuppertal
Wuppertal, Germany
Ospedale Civile SS. Antonio e Biagio di Alessandria
Alessandria, Italy
Ospedale Gen.le. Prov.le "C.G. Mazzoni"
Ascoli Piceno, Italy
Az.Ospedaliera S.G.Moscati
Avellino, Italy
Ematologia con trapianto- AOU Policlinico Consorziale di Bari
Bari, Italy
Divisione di Ematologia - Ospedali Riuniti
Bergamo, Italy
Istituto di Ematologia e Oncologia Medica "Lorenzo e A. Seragnoli" - Università degli Studi di Bologna - Policlinico S. Orsola - Malpighi
Bologna, Italy
Azienda Sanitaria di Bolzano - Ospedale Centrale - Ematologia e Centro TMO
Bolzano, Italy
Spedali Civili di Brescia
Brescia, Italy
ASL N.8 - Ospedale "A. Businco" - Unità Operativa di Ematologia e Trapianto di Midollo
Cagliari, Italy
Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto"
Catania, Italy
Azienda Ospedaliera Pugliese Ciaccio - Presidio Ospedaliero A.Pugliese - Unità Operativa di Ematologia
Catanzaro, Italy
Sezione di Ematologia e Fisiopatologia delle Emostasi - Azienda Ospedaliera - Arcispedale S. Anna
Ferrara, Italy
Divisione Ematologia 1 - Azienda Ospedaliera Universitaria "San Martino"
Genova, Italy
Divisione di Ematologia Ospedale "Santa Maria Goretti"
Latina, Italy
ST. V. Fazzi
Lecce, Italy
A.O. Universitaria Policlinico Martina di Messina
Messina, Italy
Azienda ospedaliera Papardo
Messina, Italy
IRCCS Fondazione Centro S. Raffaele del Monte Tabor
Milan, Italy
Ospedaliera "Sant' Andrea"-Università la Sapienza Seconda Facoltà di Medicina e Chirurgia
Milan, Italy
UO Centro Trapianti di Midollo - IRCCS Ospedale Maggiore Policlinico
Milan, Italy
Centro Oncologico Modenese - Dipartimento di Oncoematologia
Modena, Italy
Azienda ospedaliera S. Gerardo di Monza
Monza, Italy
A.S.L. Napoli 1 Ospedale San Giovanni Bosco
Napoli, Italy
Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli"
Napoli, Italy
Azienda Ospedaliera Universitaria - Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia
Napoli, Italy
Servizio Sanitario Nazionale - Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli" - Struttura Complessa di Ematologia - Div. TERE- 4° piano - Padiglione Palermo
Napoli, Italy
ASL SA/1 di Nocera Inferiore
Nocera Inferiore, Italy
A.O. Universitaria S. Luigi Gonzaga di Orbassano
Orbassano, Italy
Divisione di Ematologia con trapianto di midollo - A.U. Policlinico "Paolo Giaccone"
Palermo, Italy
Ospedali Riuniti "Villa Sofia-Cervello"
Palermo, Italy
Cattedra di Ematologia CTMO Università degli Studi di Parma
Parma, Italy
IRCCS Policlinico S. Matteo di Pavia
Pavia, 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
U.O. Ematologia Clinica - Azienda USL di Pescara
Pescara, Italy
Ematologia - Ospedale San Carlo
Potenza, Italy
Ospedale S. Maria delle Croci di Ravenna
Ravenna, Italy
Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli"
Reggio Calabria, Italy
IRCCS Centro di riferimento Oncologico di Basilicata
Rionero in Vulture, Italy
Azienda Osp. S. Giovanni/Addolorata
Roma, Italy
Divisione di Ematologia - Ospedale S. Camillo
Roma, Italy
Ospedale S. Eugenio
Roma, Italy
Ospedaliera "Sant' Andrea"-Università la Sapienza Seconda Facoltà di Medicina e Chirurgia
Roma, Italy
Policlinico Campus Biomedico
Roma, Italy
Policlinico Universitario Gemelli di Roma
Roma, Italy
Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia
Roma, Italy
Università degli Studi - Policlinico di Tor Vergata
Roma, Italy
IRCCS Istituto Regina Elena
Rome, 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
SCDO Ematologia 2 AOU S.Giovanni Battista
Torino, Italy
Clinica Ematologica - Policlinico Universitario
Udine, Italy
Ospedale di circolo e Fondazione Macchi
Varese, Italy
Università degli Studi di Verona - A. O. - Istituti Ospitalieri di Verona- Div. di Ematologia - Policlinico G.B. Rossi
Verona, Italy
ULSS N.6 Osp. S. Bortolo
Vicenza, Italy
Related Publications (2)
Efficace F, Mandelli F, Avvisati G, Cottone F, Ferrara F, Di Bona E, Specchia G, Breccia M, Levis A, Sica S, Finizio O, Kropp MG, Fioritoni G, Cerqui E, Vignetti M, Amadori S, Schlenk RF, Platzbecker U, Lo-Coco F. Randomized phase III trial of retinoic acid and arsenic trioxide versus retinoic acid and chemotherapy in patients with acute promyelocytic leukemia: health-related quality-of-life outcomes. J Clin Oncol. 2014 Oct 20;32(30):3406-12. doi: 10.1200/JCO.2014.55.3453. Epub 2014 Sep 22.
PMID: 25245446DERIVEDLo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S, Ferrara F, Fazi P, Cicconi L, Di Bona E, Specchia G, Sica S, Divona M, Levis A, Fiedler W, Cerqui E, Breccia M, Fioritoni G, Salih HR, Cazzola M, Melillo L, Carella AM, Brandts CH, Morra E, von Lilienfeld-Toal M, Hertenstein B, Wattad M, Lubbert M, Hanel M, Schmitz N, Link H, Kropp MG, Rambaldi A, La Nasa G, Luppi M, Ciceri F, Finizio O, Venditti A, Fabbiano F, Dohner K, Sauer M, Ganser A, Amadori S, Mandelli F, Dohner H, Ehninger G, Schlenk RF, Platzbecker U; Gruppo Italiano Malattie Ematologiche dell'Adulto; German-Austrian Acute Myeloid Leukemia Study Group; Study Alliance Leukemia. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013 Jul 11;369(2):111-21. doi: 10.1056/NEJMoa1300874.
PMID: 23841729DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Francesco Lo Coco, MD
Azienda Ospedaliera Universitaria Policlinico Tor Vergata
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 4, 2007
First Posted
June 5, 2007
Study Start
August 1, 2007
Primary Completion
September 1, 2012
Study Completion
October 17, 2019
Last Updated
October 12, 2022
Record last verified: 2022-10