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

Information source: PETHEMA Foundation
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Acute Promyelocytic Leukemia

Intervention: ATRA (Drug); Idarubicina (Drug); Mitoxantrone (Drug); ARA-C (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: PETHEMA Foundation

Official(s) and/or principal investigator(s):
San Miguel Miguel Angel, Dr, Study Chair, Affiliation: HOSPITAL LA FE VALENCIA
Vellenga Edo, Dr, Study Director, Affiliation: Stichting Hemato-Oncologie voor Volwassenen Nederland
Lowenberg Bob, Dr, Study Director, Affiliation: Stichting Hemato-Oncologie voor Volwassenen Nederland

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.

Clinical Details

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).

Study design: Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

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.

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

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

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

Eligibility

Minimum age: N/A. Maximum age: 75 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- 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 Exclusion Criteria:

- 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.

- 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.

Locations and Contacts

PALG, Lodz, Poland

Hospital General, Albacete, Spain

Hospital general, Alicante, Spain

Hospital germans Trias i Pujol, Badalona, Spain

Hospital Clinic, Barcelona, Spain

Hospital de Sant Pau, Barcelona, Spain

Institut Català d'Oncologái, Barcelona, Spain

Basurtuko Ospitalea, Bilbao, Spain

Hospital general, Castellon, Spain

Hospital de Fuenlabrada, Fuenlabrada, Spain

Hospital "Dr. Trueta", Gerona, Spain

Hospital de Jerez de la Frontera, Jerez de la Frontera, Spain

Hospital Juan Canalejo, La Coruña, Spain

Hospital Insular de las Palmas, Las Palmas de Gran Canaria, Spain

Complejo Hospitalario León, Leon, Spain

Complexo Hospitalario Xeral-Calde, Lugo, Spain

Hospital 12 de Octubre, Madrid, Spain

Hospital Clínico San Carlos, Madrid, Spain

Hospital Puerta de Hierro, Madrid, Spain

Hospital Reina Sofia, Madrid, Spain

Hospital San Pedro de Alcántara, Madrid, Spain

Hospital Severo Ochoa, Madrid, Spain

Hospital Sta. Maria del Rosell, Murcia, Spain

H. Carlos Haya, Málaga, Spain

H. Universitario Virgen de la Victoria, Málaga, Spain

Hospital Central de Asturias, Oviedo, Spain

Hospital Dr Negrín, Palma de Gran Canaria, Spain

Hospital de Navarra, Pamplona, Spain

Hospital de Montecelo, Pontevedra, Spain

Hospital Clínico Universitario, Salamanca, Spain

Hospital de Cruces, Santander, Spain

Hospital de Santiago de Compostela, Santiago de Compostela, Spain

H.U. Virgen del Rocio, Sevilla, Spain

Hospital Joan XXIII, Tarragona, Spain

Hospital Dr. Peset, Valencia, Spain

Hospital general, Valencia, Spain

Hospital La Fe, Valencia, Spain

Hospital Clínico de Valladolid, Valladolid, Spain

Hospital Txagorritxu, Vitoria, Spain

Hospital Virgen de la Concha, Zamora, Spain

Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain

Hospital Maciel, Montevideo, Uruguay

Additional Information

Spanish association of Haematology

Hovon Data Center

Related publications:

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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. Review.

Sanz MA, Martín 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. Review.

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Starting date: July 2005
Last updated: October 27, 2014

Page last updated: August 23, 2015

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