Phase III Trial in Acute Promyelocytic Leukemia Patients

Phase 3

Completed

• Conditions: Leukemia
• Interventions: Drug: arsenic trioxide; Drug: idarubicin; Drug: all-trans retinoic acid (ATRA); Drug: mercaptopurine; Drug: methotrexate; Drug: all-trans retinoic acid

• Registration Number: NCT00482833
• Lead Sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto

Brief Summary

Open label, randomised, phase III multicenter trial.

Detailed Description

* Arm I:

* Induction therapy: Patients receive oral tretinoin twice daily and arsenic trioxide IV over 2 hours on days 1-60. Patients achieving hematological complete remission go on to receive consolidation therapy.

* Consolidation therapy: Patients receive oral tretinoin twice daily on days 1-14. Treatment with tretinoin repeats every 4 weeks for up to 7 courses. Patients also receive arsenic trioxide IV over 2 hours on days 1-5 in weeks 1-4. Treatment with arsenic trioxide repeats every 8 weeks for up to 4 courses.

* Arm II:

* Induction therapy: Patients receive tretinoin as in arm I induction therapy and idarubicin IV over 20 minutes on days 2, 4, 6, and 8. Patients achieving hematological complete remission go on to receive consolidation therapy.

* Consolidation therapy: Patients receive oral tretinoin twice daily on days 1-45, idarubicin IV over 20 minutes on days 1-4 and day 31, and mitoxantrone hydrochloride IV over 30 minutes on days 16-20.

Marrow samples are collected after completion of consolidation therapy and analyzed by reverse transcriptase-PCR for molecular remission. Patients achieving molecular remission (PML-RARa negative) go on to receive maintenance therapy.

* Maintenance therapy: Patients receive oral mercaptopurine once daily and methotrexate intramuscularly once weekly for 3 months. Treatment with mercaptopurine and methotrexate repeats every 3 months for 7 courses. After completion of course 1 of mercaptopurine and methotrexate, patients receive oral tretinoin once daily on days 1-15\*. Treatment with tretinoin repeats every 3 months for 6 courses.

NOTE: \*Patients do not receive mercaptopurine and methotrexate during tretinoin administration.

After completion of study therapy, patients are followed periodically for 5 years.

As of 14th September 2010, all patients needed to evaluate the primary endpoint (162 patients) have been recruited but the trial accrual continued in order to assess one secondary outcome (QoL)."

Study Timeline

• Study First Submitted: 2007-06-04
• Study First Submitted QC: 2007-06-04
• Study First Posted: 2007-06-05
• Study Start: 2007-08
• Primary Completion: 2012-09
• Study Completion: 2019-10-17
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-10
• Last Update Posted: 2022-10-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 276

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ARM A - ATO/ATRA	all-trans retinoic acid (ATRA)	-
ARM A - ATO/ATRA	arsenic trioxide	-
ARM B - ATRA	idarubicin	-
ARM B - ATRA	methotrexate	-
ARM B - ATRA	mercaptopurine	-
ARM B - ATRA	all-trans retinoic acid	-

Primary Outcome Measures

Name	Time	Method
Event-free survival	At maximum 3.5 years from study entry	As of 14th september 2010, all patients needed to evaluate the primary endpoint have been recruited.

Secondary Outcome Measures

Name	Time	Method
Rate of cumulative incidence of relapse	At 2 years from study entry
Quality of life at the end of induction therapy and at the end of the 3rd consolidation course	At maximum 60 days from induction therapy start and at maximum 225 days from consolidation therapy start
Event free survival	At 2 years from study entry
Total hospitalization days during study therapy	At maximum 3.5 years from study entry
Overall survival rate	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
Assessment of acute promyelocytic leukemia/RARa transcript level reduction after induction and during consolidation therapy	At maximum 60 days from induction therapy start and at maximum 225 days from consolidation therapy start
Event-free survival rate in the two arms	At 2 years from study entry
Rate of hematological complete remission	At maximum 60 days from induction therapy start

Trial Locations

Locations (109)

Universitätsklinik Innsbruck Hämatologie Onkologie; 🇦🇹 Innsbruck, Austria

Krankenhaus der Barmherzigen Schwestern Linz; 🇦🇹 Linz, Austria

Universitätsklinik für Innere Medizin III Salzburg; 🇦🇹 Salzburg, Austria

Ev. Diakonie-Krankenhaus gGmbH Bremen; 🇩🇪 Bremen, Germany

Uniklinikum Erlangen; 🇩🇪 Erlangen, Germany

Universitätsklinikum Essen; 🇩🇪 Essen, Germany

Uniklinik Frankfurt/Main; 🇩🇪 Frankfurt/Main, Germany

Johannes Wesling Klinikum Minden; 🇩🇪 Minden, Germany

Klinikum der Johannes Gutenberg Universität Mainz; 🇩🇪 Mainz, Germany

Universitätsklinikum Gießen und Marburg GmbH Marburg; 🇩🇪 Marburg, Germany

Carl-von-Basedow-Klinikum Merseburg; 🇩🇪 Merseburg, Germany

Klinikum Stuttgart Bürgerhospital; 🇩🇪 Stuttgart, Germany

Robert Bosch Krankenhaus Stuttgart; 🇩🇪 Stuttgart, Germany

Krankenhaus der Barmherzigen Brüder Trier; 🇩🇪 Trier, Germany

Universitätsklinikum Ulm; 🇩🇪 Ulm, Germany

IRCCS Istituto Regina Elena; 🇮🇹 Rome, Italy

Klinikum Bremen-Mitte gGmbH; 🇩🇪 Bremen, Germany

Charité Campus Benjamin Franklin Berlin; 🇩🇪 Berlin, Germany

Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto"; 🇮🇹 Catania, Italy

Divisione Ematologia 1 - Azienda Ospedaliera Universitaria "San Martino"; 🇮🇹 Genova, Italy

UO Centro Trapianti di Midollo - IRCCS Ospedale Maggiore Policlinico; 🇮🇹 Milano, Italy

Centro Oncologico Modenese - Dipartimento di Oncoematologia; 🇮🇹 Modena, Italy

Servizio Sanitario Nazionale - Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli" - Struttura Complessa di Ematologia - Div. TERE- 4° piano - Padiglione Palermo; 🇮🇹 Napoli, Italy

Divisione di Ematologia con trapianto di midollo - A.U. Policlinico "Paolo Giaccone"; 🇮🇹 Palermo, 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

IRCCS Centro di riferimento Oncologico di Basilicata; 🇮🇹 Rionero in Vulture, Italy

Ospedale S. Eugenio; 🇮🇹 Roma, Italy

Serv. di Ematologia Ist. di Ematologia ed Endocrinologia; 🇮🇹 Sassari, Italy

Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia; 🇮🇹 Roma, Italy

Università degli Studi - Policlinico di Tor Vergata; 🇮🇹 Roma, Italy

U.O.C. Ematologia e Trapianti - A.O. Senese - Policlinico " Le Scotte"; 🇮🇹 Siena, Italy

Klinikum Bayreuth GmbH; 🇩🇪 Bayreuth, Germany

Städt. Kliniken Bielefeld gem. GmbH; 🇩🇪 Bielefeld, Germany

Universitätsklinikum Bonn; 🇩🇪 Bonn, Germany

Klinikum Chemnitz gGmbH; 🇩🇪 Chemnitz, Germany

Universitätsklinikum C. G. Carus Dresden; 🇩🇪 Dresden, Germany

Kliniken Essen Süd, Ev. Krankenhaus Essen-Werden gGmbH; 🇩🇪 Essen, Germany

Katholisches Klinikum Duisburg St. Johannes Hospital; 🇩🇪 Duisburg, Germany

Universitätsklinikum Düsseldorf; 🇩🇪 Düsseldorf, Germany

Klinikum Fulda; 🇩🇪 Fulda, Germany

Städtische Kliniken Frankfurt a. M.-Höchst; 🇩🇪 Frankfurt/a. M. -Höchst, Germany

Universitätsklinikum Gießen und Marburg Gießen; 🇩🇪 Gießen, Germany

Universitätsklinikum Freiburg; 🇩🇪 Freiburg, Germany

Universitätsklinikum Göttingen; 🇩🇪 Göttingen, Germany

Universitätsklinikum Hamburg Eppendorf; 🇩🇪 Hamburg, Germany

St. Marien-Hospital gem. GmbH Hamm; 🇩🇪 Hamm, Germany

St. Bernward Krankenhaus Hildesheim; 🇩🇪 Hildesheim, Germany

Universitätsklinikum Heidelberg; 🇩🇪 Heidelberg, Germany

Asklepios Klinik Hamburg Altona; 🇩🇪 Hamburg, Germany

Asklepios Klinik St. Georg Hamburg; 🇩🇪 Hamburg, Germany

Medizinische Hochschule Hannover; 🇩🇪 Hannover, Germany

Universitätsklinikum des Saarlandes Homburg/Saar; 🇩🇪 Homburg, Germany

Klinik für Knochenmarktransplantation und Hämatologie Idar-Oberstein; 🇩🇪 Idar-Oberstein, Germany

Westpfalz-Klinikum GmbH Kaiserslautern; 🇩🇪 Kaiserslautern, Germany

Klinikum Lippe Lemgo; 🇩🇪 Lippe, Germany

Caritas-Krankenhaus Lebach; 🇩🇪 Lebach, Germany

Klinikum rechts der Isar (München); 🇩🇪 München, Germany

Uniklinikum Lübeck; 🇩🇪 Lübeck, Germany

Klinikum Nord Nürnberg; 🇩🇪 Nürnberg, Germany

Klinikum Passau; 🇩🇪 Passau, Germany

Diakonie-Krankenhaus Schwäbisch Hall; 🇩🇪 Schwäbisch-Hall, Germany

Caritas-Klinik St. Theresia Saarbrücken; 🇩🇪 Saarbrücken, Germany

Universitätsklinikum Regensburg; 🇩🇪 Regensburg, Germany

Diakonie-Klinikum Stuttgart; 🇩🇪 Stuttgart, Germany

Krankenanstalt Mutterhaus der Borromäerinnen Trier; 🇩🇪 Trier, Germany

Universitätsklinikum Tübingen; 🇩🇪 Tübingen, 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

Azienda Sanitaria di Bolzano - Ospedale Centrale - Ematologia e Centro TMO; 🇮🇹 Bolzano, Italy

Spedali Civili di Brescia; 🇮🇹 Brescia, Italy

Sezione di Ematologia e Fisiopatologia delle Emostasi - Azienda Ospedaliera - Arcispedale S. Anna; 🇮🇹 Ferrara, Italy

Istituto di Ematologia e Oncologia Medica "Lorenzo e A. Seragnoli" - Università degli Studi di Bologna - Policlinico S. Orsola - Malpighi; 🇮🇹 Bologna, Italy

ASL N.8 - Ospedale "A. Businco" - Unità Operativa di Ematologia e Trapianto di Midollo; 🇮🇹 Cagliari, Italy

Azienda Ospedaliera Pugliese Ciaccio - Presidio Ospedaliero A.Pugliese - Unità Operativa di Ematologia; 🇮🇹 Catanzaro, Italy

ST. V. Fazzi; 🇮🇹 Lecce, Italy

A.O. Universitaria Policlinico Martina di Messina; 🇮🇹 Messina, Italy

Divisione di Ematologia Ospedale "Santa Maria Goretti"; 🇮🇹 Latina, Italy

Ospedaliera "Sant' Andrea"-Università la Sapienza Seconda Facoltà di Medicina e Chirurgia; 🇮🇹 Roma, Italy

Azienda ospedaliera Papardo; 🇮🇹 Messina, Italy

IRCCS Fondazione Centro S. Raffaele del Monte Tabor; 🇮🇹 Milano, Italy

Azienda ospedaliera S. Gerardo di Monza; 🇮🇹 Monza, 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

ASL SA/1 di Nocera Inferiore; 🇮🇹 Nocera Inferiore, Italy

A.S.L. Napoli 1 Ospedale San Giovanni Bosco; 🇮🇹 Napoli, Italy

A.O. Universitaria S. Luigi Gonzaga di Orbassano; 🇮🇹 Orbassano, Italy

IRCCS Policlinico S. Matteo di Pavia; 🇮🇹 Pavia, Italy

Ospedali Riuniti "Villa Sofia-Cervello"; 🇮🇹 Palermo, Italy

Cattedra di Ematologia CTMO Università degli Studi di Parma; 🇮🇹 Parma, Italy

U.O. Ematologia Clinica - Azienda USL di Pescara; 🇮🇹 Pescara, Italy

Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli"; 🇮🇹 Reggio Calabria, Italy

Ematologia - Ospedale San Carlo; 🇮🇹 Potenza, Italy

Ospedale S. Maria delle Croci di Ravenna; 🇮🇹 Ravenna, Italy

Azienda Osp. S. Giovanni/Addolorata; 🇮🇹 Roma, Italy

Divisione di Ematologia - Ospedale S. Camillo; 🇮🇹 Roma, Italy

Policlinico Universitario Gemelli di Roma; 🇮🇹 Roma, Italy

Policlinico Campus Biomedico; 🇮🇹 Roma, Italy

Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza; 🇮🇹 San Giovanni Rotondo, Italy

Università degli Studi di Verona - A. O. - Istituti Ospitalieri di Verona- Div. di Ematologia - Policlinico G.B. Rossi; 🇮🇹 Verona, Italy

Ospedale di circolo e Fondazione Macchi; 🇮🇹 Varese, Italy

ULSS N.6 Osp. S. Bortolo; 🇮🇹 Vicenza, Italy

SCDO Ematologia 2 AOU S.Giovanni Battista; 🇮🇹 Torino, Italy

Clinica Ematologica - Policlinico Universitario; 🇮🇹 Udine, Italy