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

Conditions

Acute Promyelocytic Leukemia

Keywords

Acute Promyelocytic Leukemia

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

Sanz MA, Montesinos P, Kim HT, Ruiz-Argüelles GJ, Undurraga MS, Uriarte MR, Martínez L, Jacomo RH, Gutiérrez-Aguirre H, Melo RA, Bittencourt R, Pasquini R, Pagnano K, Fagundes EM, Vellenga E, Holowiecka A, González-Huerta AJ, Fernández P, De la Serna J, Brunet S, De Lisa E, González-Campos J, Ribera JM, Krsnik I, Ganser A, Berliner N, Ribeiro RC, Lo-Coco F, Löwenberg B, Rego EM, IC-APL and PETHEMA and HOVON Groups.

2015-05-1523 citations

10.1007/s00277-015-2393-0

Clinical significance of CD56 expression in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline-based regimens.

Montesinos P, Rayón C, Vellenga E, Brunet S, González J, González M, Holowiecka A, Esteve J, Bergua J, González JD, Rivas C, Tormo M, Rubio V, Bueno J, Manso F, Milone G, de la Serna J, Pérez I, Pérez-Encinas M, Krsnik I, Ribera JM, Escoda L, Lowenberg B, Sanz MA, PETHEMA, HOVON Groups.

2010-12-0894 citations

10.1182/blood-2010-04-277434

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.

Sanz MA, Montesinos P, Rayón C, Holowiecka A, de la Serna J, Milone G, de Lisa E, Brunet S, Rubio V, Ribera JM, Rivas C, Krsnik I, Bergua J, González J, Díaz-Mediavilla J, Rojas R, Manso F, Ossenkoppele G, González JD, Lowenberg B, PETHEMA and HOVON Groups.

2010-04-14232 citations

10.1182/blood-2010-01-266007

Interventions

DRUGATRA

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

DRUGIdarubicina

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.

DRUGMitoxantrone

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

DRUGARA-C

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

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

No minimum to 75 Years

Healthy volunteers

No

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.

Design outcomes

Primary

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

Measure	Time frame
To compare all outcomes with those achieved with the PETHEMA LPA99 protocol.	2 years

Countries

Poland, Spain, Uruguay

Outcome results

None listed