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).

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

Sponsors

Lead sponsor: PETHEMA Foundation

Source PETHEMA Foundation
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

Overall Status Completed
Start Date July 2005
Completion Date December 2013
Primary Completion Date April 2012
Phase Phase 4
Study Type Interventional
Primary Outcome
Measure Time Frame
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 Outcome
Measure Time Frame
To compare all outcomes with those achieved with the PETHEMA LPA99 protocol. 2 years
Enrollment 300
Condition
Intervention

Intervention type: Drug

Intervention name: ATRA

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

Intervention type: Drug

Intervention name: Idarubicina

Description: 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.

Intervention type: Drug

Intervention name: Mitoxantrone

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

Intervention type: Drug

Intervention name: ARA-C

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

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.

Gender: All

Minimum age: N/A

Maximum age: 75 Years

Healthy volunteers: No

Overall Official
Location
facility
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
Location Countries

Poland

Spain

Uruguay

Verification Date

October 2014

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Study Design Info

Allocation: Non-Randomized

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov