Treatment of Newly Diagnosed Patients With Acute Promyelocytic Leukemia (PETHEMA LPA 2005)

NCT00408278 | Completed Phase 4

• 1 other identifier: LPA 2005
• Study Type: interventional
• Target: 300
• Locations: 3 countries
• Sites: 42

Brief Summary

Primary objectives

• To evaluate the efficacy and toxicity of a risk-adapted protocol that use idarubicin for induction and consolidation therapy in patients with APL.
• To evaluate the impact of mitoxantrone reduction on the event-free, disease-free, and overall survival, as well as on the duration of remission and cumulative incidence of relapse in low- and intermediate-risk patients with APL.
• To evaluate the impact of the addition of ara-C to idarubicin courses of consolidation for high-risk patients (administered as in the original GIMEMA protocols) on the event-free, disease-free, and overall survival, as well as on the duration of remission and cumulative incidence of relapse.
• To evaluate the toxicity of the induction, consolidation, and maintenance chemotherapy in the whole series and in each treatment group in patients with APL. Secondary objectives
• To compare all outcomes with those achieved with the PETHEMA LPA99 protocol.

Conditions

Acute Promyelocytic Leukemia

Keywords

Acute Promyelocytic Leukemia

Outcome Measures

Primary Outcomes (4)

• To evaluate the efficacy and toxicity of a risk-adapted protocol that use idarubicin for induction and consolidation therapy in patients with APL.

  1 year

• To evaluate the impact of mitoxantrone reduction on the event-free, disease-free, and overall survival.

  1 year

• To evaluate the impact of the addition of ara-C to idarubicin courses of consolidation for high-risk patients on the event-free, disease-free, and overall survival

  1 year

• To evaluate the toxicity of the induction, consolidation, and maintenance chemotherapy in the whole series and in each treatment group in patients with APL.

  1 year

Secondary Outcomes (1)

• To compare all outcomes with those achieved with the PETHEMA LPA99 protocol.

  2 years

Interventions

ATRA DRUG

45 mg/m2 day until CR Consolidation: 3 cycles (45 mg/m2 days 1-15) Maintenance:15 days every 3 months

Idarubicina DRUG

Induction: 12 mg/m2 days 2, 4, 6 and 8 Consolidation: 5 mg/m2 days 1-4 in cycle 1 and 12 mg/m2 day 1 in cycle 3.

Mitoxantrone DRUG

Consolidation: Mitoxantrone 10 mg/m2 days 1-3 in cycle 2

ARA-C DRUG

In high risk patients, consolidation with ara-C in cycles 1 and 3.

Eligibility Criteria

• Age: Up to 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≤ 75 years.
• ECOG ≤ 3.
• Morphologic Diagnosis of LPA (FAB M3 or variant M3). Those cases without typical morphology but with PML-RARα reordering also must be including.
• Genetic Diagnosis: t (15; 17) demonstrated by cariotipo conventional, FISH, PML-RARα reordering detected by RT-PCR or a pattern microspeckled demonstrated with antibody anti-PML (positive PGM3). Obvious, it will be had the result of these tests once initiated the treatment on the basis of a suspicion diagnoses morphologic

You may not qualify if:

• Age \>75 years (the treatment with this protocol can be considered individually)
• Absence of PML-Rare reordering.
• To have received chemotherapy or x-ray for the treatment of a disease vitiates previous.
• Associate Neoplasia.
• Serious psychiatric Disease.
• Seropositividad for VIH.
• Contraindication to receive intensive chemotherapy, specially antraciclinas.
• Sérica Creatinina ≥ 2,5 mg/dL (≥ 250 μmol/l).
• Bilirrubina, fosfatasa alkaline, or GOT \> 3 times the normal limit
• Test of positive pregnancy.

Sponsors & Collaborators

• PETHEMA Foundation: lead

Study Sites (42)

PALG

Lodz, Poland

Location

Hospital Juan Canalejo

A Coruña, Spain

Location

Hospital General

Albacete, Spain

Location

Hospital general

Alicante, Spain

Location

Hospital germans Trias i Pujol

Badalona, Spain

Location

Hospital Clinic

Barcelona, Spain

Location

Hospital de Sant Pau

Barcelona, Spain

Location

Institut Català d'Oncologái

Barcelona, Spain

Location

Basurtuko Ospitalea

Bilbao, Spain

Location

Hospital general

Castellon, Spain

Location

Hospital de Fuenlabrada

Fuenlabrada, Spain

Location

Hospital "Dr. Trueta"

Girona, Spain

Location

Hospital de Jerez de la Frontera

Jerez de la Frontera, Spain

Location

Hospital Insular de las Palmas

Las Palmas de Gran Canaria, Spain

Location

Complejo Hospitalario León

León, Spain

Location

Complexo Hospitalario Xeral-Calde

Lugo, Spain

Location

Hospital 12 de Octubre

Madrid, Spain

Location

Hospital Clínico San Carlos

Madrid, Spain

Location

Hospital Puerta de Hierro

Madrid, Spain

Location

Hospital Reina Sofia

Madrid, Spain

Location

Hospital San Pedro de Alcántara

Madrid, Spain

Location

Hospital Severo Ochoa

Madrid, Spain

Location

H. Carlos Haya

Málaga, Spain

Location

H. Universitario Virgen de la Victoria

Málaga, Spain

Location

Hospital Sta. Maria del Rosell

Murcia, Spain

Location

Hospital Central de Asturias

Oviedo, Spain

Location

Hospital Dr Negrín

Palma de Gran Canaria, Spain

Location

Hospital de Navarra

Pamplona, Spain

Location

Hospital de Montecelo

Pontevedra, Spain

Location

Hospital Clínico Universitario

Salamanca, Spain

Location

Hospital de Cruces

Santander, Spain

Location

Hospital de Santiago de Compostela

Santiago de Compostela, Spain

Location

H.U. Virgen del Rocio

Seville, Spain

Location

Hospital Joan XXIII

Tarragona, Spain

Location

Hospital Dr. Peset

Valencia, Spain

Location

Hospital general

Valencia, Spain

Location

Hospital La Fe

Valencia, Spain

Location

Hospital Clínico de Valladolid

Valladolid, Spain

Location

Hospital Txagorritxu

Vitoria-Gasteiz, Spain

Location

Hospital Virgen de la Concha

Zamora, Spain

Location

Hospital Clínico Universitario Lozano Blesa

Zaragoza, Spain

Location

Hospital Maciel

Montevideo, Uruguay

Location

Related Publications (17)

• Tallman MS, Nabhan C, Feusner JH, Rowe JM. Acute promyelocytic leukemia: evolving therapeutic strategies. Blood. 2002 Feb 1;99(3):759-67. doi: 10.1182/blood.v99.3.759.

  PMID: 11806975 BACKGROUND

• Ohno R, Asou N, Ohnishi K. Treatment of acute promyelocytic leukemia: strategy toward further increase of cure rate. Leukemia. 2003 Aug;17(8):1454-63. doi: 10.1038/sj.leu.2403031.

  PMID: 12886231 BACKGROUND

• Sanz MA, Martin G, Lo Coco F. Choice of chemotherapy in induction, consolidation and maintenance in acute promyelocytic leukaemia. Best Pract Res Clin Haematol. 2003 Sep;16(3):433-51. doi: 10.1016/s1521-6926(03)00040-9.

  PMID: 12935961 BACKGROUND

• Asou N, Adachi K, Tamura J, Kanamaru A, Kageyama S, Hiraoka A, Omoto E, Akiyama H, Tsubaki K, Saito K, Kuriyama K, Oh H, Kitano K, Miyawaki S, Takeyama K, Yamada O, Nishikawa K, Takahashi M, Matsuda S, Ohtake S, Suzushima H, Emi N, Ohno R. Analysis of prognostic factors in newly diagnosed acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy. Japan Adult Leukemia Study Group. J Clin Oncol. 1998 Jan;16(1):78-85. doi: 10.1200/JCO.1998.16.1.78.

  PMID: 9440726 BACKGROUND

• Burnett AK, Grimwade D, Solomon E, Wheatley K, Goldstone AH. Presenting white blood cell count and kinetics of molecular remission predict prognosis in acute promyelocytic leukemia treated with all-trans retinoic acid: result of the Randomized MRC Trial. Blood. 1999 Jun 15;93(12):4131-43.

  PMID: 10361110 BACKGROUND

• Fenaux P, Chastang C, Chevret S, Sanz M, Dombret H, Archimbaud E, Fey M, Rayon C, Huguet F, Sotto JJ, Gardin C, Makhoul PC, Travade P, Solary E, Fegueux N, Bordessoule D, Miguel JS, Link H, Desablens B, Stamatoullas A, Deconinck E, Maloisel F, Castaigne S, Preudhomme C, Degos L. A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. The European APL Group. Blood. 1999 Aug 15;94(4):1192-200.

  PMID: 10438706 BACKGROUND

• Lengfelder E, Reichert A, Schoch C, Haase D, Haferlach T, Loffler H, Staib P, Heyll A, Seifarth W, Saussele S, Fonatsch C, Gassmann W, Ludwig WD, Hochhaus A, Beelen D, Aul C, Sauerland MC, Heinecke A, Hehlmann R, Wormann B, Hiddemann W, Buchner T. Double induction strategy including high dose cytarabine in combination with all-trans retinoic acid: effects in patients with newly diagnosed acute promyelocytic leukemia. German AML Cooperative Group. Leukemia. 2000 Aug;14(8):1362-70. doi: 10.1038/sj.leu.2401843.

  PMID: 10942230 BACKGROUND

• Sanz MA, Lo Coco F, Martin G, Avvisati G, Rayon C, Barbui T, Diaz-Mediavilla J, Fioritoni G, Gonzalez JD, Liso V, Esteve J, Ferrara F, Bolufer P, Bernasconi C, Gonzalez M, Rodeghiero F, Colomer D, Petti MC, Ribera JM, Mandelli F. Definition of relapse risk and role of nonanthracycline drugs for consolidation in patients with acute promyelocytic leukemia: a joint study of the PETHEMA and GIMEMA cooperative groups. Blood. 2000 Aug 15;96(4):1247-53.

  PMID: 10942364 BACKGROUND

• Sanz MA, Martin G, Gonzalez M, Leon A, Rayon C, Rivas C, Colomer D, Amutio E, Capote FJ, Milone GA, De La Serna J, Roman J, Barragan E, Bergua J, Escoda L, Parody R, Negri S, Calasanz MJ, Bolufer P; Programa de Estudio y Traitmiento de las Hemopatias Malignas. Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood. 2004 Feb 15;103(4):1237-43. doi: 10.1182/blood-2003-07-2462. Epub 2003 Oct 23.

  PMID: 14576047 BACKGROUND

• Grimwade D, Gorman P, Duprez E, Howe K, Langabeer S, Oliver F, Walker H, Culligan D, Waters J, Pomfret M, Goldstone A, Burnett A, Freemont P, Sheer D, Solomon E. Characterization of cryptic rearrangements and variant translocations in acute promyelocytic leukemia. Blood. 1997 Dec 15;90(12):4876-85.

  PMID: 9389704 BACKGROUND

• van Dongen JJ, Macintyre EA, Gabert JA, Delabesse E, Rossi V, Saglio G, Gottardi E, Rambaldi A, Dotti G, Griesinger F, Parreira A, Gameiro P, Diaz MG, Malec M, Langerak AW, San Miguel JF, Biondi A. Standardized RT-PCR analysis of fusion gene transcripts from chromosome aberrations in acute leukemia for detection of minimal residual disease. Report of the BIOMED-1 Concerted Action: investigation of minimal residual disease in acute leukemia. Leukemia. 1999 Dec;13(12):1901-28. doi: 10.1038/sj.leu.2401592.

  PMID: 10602411 BACKGROUND

• Falini B, Flenghi L, Fagioli M, Lo Coco F, Cordone I, Diverio D, Pasqualucci L, Biondi A, Riganelli D, Orleth A, Liso A, Martelli MF, Pelicci PG, Pileri S. Immunocytochemical diagnosis of acute promyelocytic leukemia (M3) with the monoclonal antibody PG-M3 (anti-PML). Blood. 1997 Nov 15;90(10):4046-53.

  PMID: 9354674 BACKGROUND

• Gomis F, Sanz J, Sempere A, Plume G, Senent ML, Perez ML, Cervera J, Moscardo F, Bolufer P, Barragan E, Martin G, Sanz MA. Immunofluorescent analysis with the anti-PML monoclonal antibody PG-M3 for rapid and accurate genetic diagnosis of acute promyelocytic leukemia. Ann Hematol. 2004 Nov;83(11):687-90. doi: 10.1007/s00277-004-0902-7. Epub 2004 Jul 24.

  PMID: 15278297 BACKGROUND

• Martinez-Cuadron D, Montesinos P, Vellenga E, Bernal T, Salamero O, Holowiecka A, Brunet S, Gil C, Benavente C, Ribera JM, Perez-Encinas M, De la Serna J, Esteve J, Rubio V, Gonzalez-Campos J, Escoda L, Amutio ME, Arnan M, Arias J, Negri S, Lowenberg B, Sanz MA. Long-term outcome of older patients with newly diagnosed de novo acute promyelocytic leukemia treated with ATRA plus anthracycline-based therapy. Leukemia. 2018 Jan;32(1):21-29. doi: 10.1038/leu.2017.178. Epub 2017 Jun 6.

  PMID: 28584252 DERIVED

• Sanz MA, Montesinos P, Kim HT, Ruiz-Arguelles GJ, Undurraga MS, Uriarte MR, Martinez L, Jacomo RH, Gutierrez-Aguirre H, Melo RA, Bittencourt R, Pasquini R, Pagnano K, Fagundes EM, Vellenga E, Holowiecka A, Gonzalez-Huerta AJ, Fernandez P, De la Serna J, Brunet S, De Lisa E, Gonzalez-Campos J, Ribera JM, Krsnik I, Ganser A, Berliner N, Ribeiro RC, Lo-Coco F, Lowenberg B, Rego EM; IC-APL and PETHEMA and HOVON Groups. All-trans retinoic acid with daunorubicin or idarubicin for risk-adapted treatment of acute promyelocytic leukaemia: a matched-pair analysis of the PETHEMA LPA-2005 and IC-APL studies. Ann Hematol. 2015 Aug;94(8):1347-56. doi: 10.1007/s00277-015-2393-0. Epub 2015 May 15.

  PMID: 25975975 DERIVED

• Montesinos P, Rayon C, Vellenga E, Brunet S, Gonzalez J, Gonzalez M, Holowiecka A, Esteve J, Bergua J, Gonzalez JD, Rivas C, Tormo M, Rubio V, Bueno J, Manso F, Milone G, de la Serna J, Perez I, Perez-Encinas M, Krsnik I, Ribera JM, Escoda L, Lowenberg B, Sanz MA; PETHEMA; HOVON Groups. Clinical significance of CD56 expression in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline-based regimens. Blood. 2011 Feb 10;117(6):1799-805. doi: 10.1182/blood-2010-04-277434. Epub 2010 Dec 8.

  PMID: 21148082 DERIVED

• Sanz MA, Montesinos P, Rayon C, Holowiecka A, de la Serna J, Milone G, de Lisa E, Brunet S, Rubio V, Ribera JM, Rivas C, Krsnik I, Bergua J, Gonzalez J, Diaz-Mediavilla J, Rojas R, Manso F, Ossenkoppele G, Gonzalez JD, Lowenberg B; PETHEMA and HOVON Groups. Risk-adapted treatment of acute promyelocytic leukemia based on all-trans retinoic acid and anthracycline with addition of cytarabine in consolidation therapy for high-risk patients: further improvements in treatment outcome. Blood. 2010 Jun 24;115(25):5137-46. doi: 10.1182/blood-2010-01-266007. Epub 2010 Apr 14.

  PMID: 20393132 DERIVED

Related Links

• Spanish association of Haematology
• Hovon Data Center

MeSH Terms

Conditions

Leukemia, Promyelocytic, Acute

Interventions

Idarubicin; Mitoxantrone; Cytarabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Anthraquinones; Anthrones; Anthracenes; Quinones; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• San Miguel Miguel Angel, Dr

  Hospital La Fe de Valencia

  STUDY CHAIR

• Vellenga Edo, Dr

  Stichting Hemato-Oncologie voor Volwassenen Nederland

  STUDY DIRECTOR

• Lowenberg Bob, Dr

  Stichting Hemato-Oncologie voor Volwassenen Nederland

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2006
• First Posted: December 6, 2006
• Study Start: July 1, 2005
• Primary Completion: April 1, 2012
• Study Completion: December 1, 2013
• Last Updated: October 28, 2014

Record last verified: 2014-10

Locations

ES (40); UR (1); PL (1)