Clinical trial NCT00408278: Treatment of Newly Diagnosed Patients With Acute Promyelocytic Leukemia (PETHEMA LPA 2005)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acute Promyelocytic Leukemia
Keywords: Acute Promyelocytic Leukemia
Lead sponsor: PETHEMA Foundation
Sponsor class: OTHER
First posted: 2006-12-06
Enrollment: 300
Sex: ALL
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
measure: To evaluate the efficacy and toxicity of a risk-adapted protocol that use idarubicin for induction and consolidation therapy in patients with APL.
timeFrame: 1 year
measure: To evaluate the impact of mitoxantrone reduction on the event-free, disease-free, and overall survival.
timeFrame: 1 year
measure: 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
timeFrame: 1 year
measure: To evaluate the toxicity of the induction, consolidation, and maintenance chemotherapy in the whole series and in each treatment group in patients with APL.
timeFrame: 1 year
Secondary outcomes:
measure: To compare all outcomes with those achieved with the PETHEMA LPA99 protocol.
timeFrame: 2 years
Other outcomes:
Locations:
city: Lodz
country: Poland
facility: PALG
city: Albacete
country: Spain
facility: Hospital General
city: Alicante
country: Spain
facility: Hospital general
city: Badalona
country: Spain
facility: Hospital germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital Clinic
city: Barcelona
country: Spain
facility: Hospital de Sant Pau
city: Barcelona
country: Spain
facility: Institut Català d'Oncologái
city: Bilbao
country: Spain
facility: Basurtuko Ospitalea
city: Castellon
country: Spain
facility: Hospital general
city: Fuenlabrada
country: Spain
facility: Hospital de Fuenlabrada
city: Gerona
country: Spain
facility: Hospital "Dr. Trueta"
city: Jerez de la Frontera
country: Spain
facility: Hospital de Jerez de la Frontera
city: La Coruña
country: Spain
facility: Hospital Juan Canalejo
city: Las Palmas de Gran Canaria
country: Spain
facility: Hospital Insular de las Palmas
city: Leon
country: Spain
facility: Complejo Hospitalario León
city: Lugo
country: Spain
facility: Complexo Hospitalario Xeral-Calde
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Puerta de Hierro
city: Madrid
country: Spain
facility: Hospital Reina Sofia
city: Madrid
country: Spain
facility: Hospital San Pedro de Alcántara
city: Madrid
country: Spain
facility: Hospital Severo Ochoa
city: Murcia
country: Spain
facility: Hospital Sta. Maria del Rosell
city: Málaga
country: Spain
facility: H. Carlos Haya
city: Málaga
country: Spain
facility: H. Universitario Virgen de la Victoria
city: Oviedo
country: Spain
facility: Hospital Central de Asturias
city: Palma de Gran Canaria
country: Spain
facility: Hospital Dr Negrín
city: Pamplona
country: Spain
facility: Hospital de Navarra
city: Pontevedra
country: Spain
facility: Hospital de Montecelo
city: Salamanca
country: Spain
facility: Hospital Clínico Universitario
city: Santander
country: Spain
facility: Hospital de Cruces
city: Santiago de Compostela
country: Spain
facility: Hospital de Santiago de Compostela
city: Sevilla
country: Spain
facility: H.U. Virgen del Rocio
city: Tarragona
country: Spain
facility: Hospital Joan XXIII
city: Valencia
country: Spain
facility: Hospital Dr. Peset
city: Valencia
country: Spain
facility: Hospital general
city: Valencia
country: Spain
facility: Hospital La Fe
city: Valladolid
country: Spain
facility: Hospital Clínico de Valladolid
city: Vitoria
country: Spain
facility: Hospital Txagorritxu
city: Zamora
country: Spain
facility: Hospital Virgen de la Concha
city: Zaragoza
country: Spain
facility: Hospital Clínico Universitario Lozano Blesa
city: Montevideo
country: Uruguay
facility: Hospital Maciel
Study officials:
affiliation: HOSPITAL LA FE VALENCIA
name: San Miguel Miguel Angel, Dr
role: STUDY_CHAIR
affiliation: Stichting Hemato-Oncologie voor Volwassenen Nederland
name: Vellenga Edo, Dr
role: STUDY_DIRECTOR
affiliation: Stichting Hemato-Oncologie voor Volwassenen Nederland
name: Lowenberg Bob, Dr
role: STUDY_DIRECTOR
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