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Acute Promyelocytic LeukemiaPhase 4NCT00408278

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

A Phase 4 study testing ATRA, Idarubicina and Mitoxantrone in people with Acute Promyelocytic Leukemia, run by PETHEMA Foundation at 42 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages Up to 75 years
Conditions the study is for
Acute Promyelocytic Leukemia
What is being tested?
ATRA, Idarubicina and Mitoxantrone
How many people
300 participants
Where
42 sitesin 3 countries
Study dates
Jul 2005to Dec 2013
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 75 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • Age >75 years (the treatment with this protocol can be considered individually)
  • Absence of PML-Rare reordering.
  • To have received previously some type of treatment for LPA, including chemotherapy or retinoides. The previous treatment with corticoids, hidroxiurea or leucoaféresis is not reason for exclusion.
  • To have received chemotherapy or x-ray for the treatment of a disease vitiates previous.
  • Associate Neoplasia.
  • Serious psychiatric Disease.
Show all 11Show fewer
  • 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.

Trial locations and contacts

42 sites in 3 countries.

42 sites in 3 countries

Spain40 sites

  • Hospital Juan Canalejo

    A Coruña

  • Hospital General

    Albacete

  • Hospital general

    Alicante

  • Hospital germans Trias i Pujol

    Badalona

  • Hospital Clinic

    Barcelona

  • Hospital de Sant Pau

    Barcelona

  • Institut Català d'Oncologái

    Barcelona

  • Basurtuko Ospitalea

    Bilbao

  • Hospital general

    Castellon

  • Hospital de Fuenlabrada

    Fuenlabrada

  • Hospital "Dr. Trueta"

    Girona

  • Hospital de Jerez de la Frontera

    Jerez de la Frontera

  • Hospital Insular de las Palmas

    Las Palmas de Gran Canaria

  • Complejo Hospitalario León

    León

  • Complexo Hospitalario Xeral-Calde

    Lugo

  • Hospital 12 de Octubre

    Madrid

  • Hospital Clínico San Carlos

    Madrid

  • Hospital Puerta de Hierro

    Madrid

  • Hospital Reina Sofia

    Madrid

  • Hospital San Pedro de Alcántara

    Madrid

  • Hospital Severo Ochoa

    Madrid

  • H. Carlos Haya

    Málaga

  • H. Universitario Virgen de la Victoria

    Málaga

  • Hospital Sta. Maria del Rosell

    Murcia

  • Hospital Central de Asturias

    Oviedo

  • Hospital Dr Negrín

    Palma de Gran Canaria

  • Hospital de Navarra

    Pamplona

  • Hospital de Montecelo

    Pontevedra

  • Hospital Clínico Universitario

    Salamanca

  • Hospital de Cruces

    Santander

  • Hospital de Santiago de Compostela

    Santiago de Compostela

  • H.U. Virgen del Rocio

    Seville

  • Hospital Joan XXIII

    Tarragona

  • Hospital Dr. Peset

    Valencia

  • Hospital general

    Valencia

  • Hospital La Fe

    Valencia

  • Hospital Clínico de Valladolid

    Valladolid

  • Hospital Txagorritxu

    Vitoria-Gasteiz

  • Hospital Virgen de la Concha

    Zamora

  • Hospital Clínico Universitario Lozano Blesa

    Zaragoza

Other trials in Spain

Poland1 site

  • PALG

    Lodz

Other trials in Poland

Uruguay1 site

  • Hospital Maciel

    Montevideo

Other trials in Uruguay

About this study

Official title: Treatment of Newly Diagnosed Patients With Acute Promyelocytic Leukemia (PETHEMA LPA 2005): Remission Induction With ATRA + Idarubicin. Risk-adapted Consolidation With ATRA and Anthracycline-based Chemotherapy (Idarubicin/Mitoxantrone) With Addition of Ara-C for High-risk Patients. Maintenance Therapy With ATRA + Low Dose Chemotherapy (Methotrexate + Mercaptopurine).

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.
Read more

Secondary objectives

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

Treatment of induction with the simultaneous administration of ATRA (45 mg/m2 day until the RC) and idarubicine (12 mg/m2 days 2, 4, 6 and 8), 3 monthly cycles of consolidation with ATRA (45 mg/m2 days 1-15) and idarubicine (5 mg/m2 days 1-4) in the cycle #1, mitoxantrone (10 mg/m2 days 1-3) in the cycle #2 and idarubicine (12 mg/m2 day 1) in the cycle #3. The consolidation was reinforced for the group of patients with intermediate risk by means of an increase of the idarubicine to 7 mg in the cycle #1 and to 2 days in the cycle #3. In the patients of high risk, the consolidation was reinforced with the addition of altar-c in the cycles #1 and #3. For the maintenance treatment, one will administer to intermittent ATRA (15 days every 3 months) and chemotherapy low doses with methotrexate and 6-mercaptopurina during two years

Being tested
ATRA, Idarubicina, Mitoxantrone, ARA-C
Keywords
Acute Promyelocytic Leukemia
Medical subject headings
Leukemia, Promyelocytic, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ATRADrug

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

  • IdarubicinaDrug

    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.

  • MitoxantroneDrug

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

  • ARA-CDrug

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

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: 1 year

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

    Measured: 1 year

  3. 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

    Measured: 1 year

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

    Measured: 1 year

Secondary outcomes (1)

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

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Dec 2006 (estimated)
  2. Study startJul 2005
  3. Primary completionApr 2012
  4. Study completionDec 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
300 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00408278
Sponsor's protocol ID
LPA 2005
Status last verified
Oct 2014
First submitted
5 Dec 2006
Last updated
28 Oct 2014
Results posted
No

Publications

  • 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.

    PubMed 11806975

  • 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.

    PubMed 12886231

  • 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.

    PubMed 12935961

  • 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.

    PubMed 9440726

  • 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.

    PubMed 10361110

  • 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.

    PubMed 10438706

  • 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.

    PubMed 10942230

  • 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.

    PubMed 10942364

  • 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.

    PubMed 14576047

  • 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.

    PubMed 9389704

  • 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.

    PubMed 10602411

  • 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.

    PubMed 9354674

  • 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.

    PubMed 15278297

  • 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.

    PubMed 28584252

  • 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.

    PubMed 25975975

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing ATRA, Idarubicina and Mitoxantrone in people with Acute Promyelocytic Leukemia, run by PETHEMA Foundation at 42 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 42 sites in Spain, Poland, Uruguay. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To evaluate the efficacy and toxicity of a risk-adapted protocol that use idarubicin for induction and consolidation therapy in patients with APL. (time frame: 1 year). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00408278, which also lists 17 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2014.

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