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

Study Overview
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Brief Summary
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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
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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

Official Title
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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).

Conditions
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Acute Promyelocytic Leukemia

Intervention / Treatment
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* Drug: ATRA
* Drug: Idarubicina
* Drug: Mitoxantrone
* Drug: ARA-C


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: ATRA|45 mg/m2 day until CR Consolidation: 3 cycles (45 mg/m2 days 1-15) Maintenance:15 days every 3 months|
|Drug: Idarubicina|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.|
|Drug: Mitoxantrone|Consolidation: Mitoxantrone 10 mg/m2 days 1-3 in cycle 2|
|Drug: ARA-C|In high risk patients, consolidation with ara-C in cycles 1 and 3.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare all outcomes with those achieved with the PETHEMA LPA99 protocol. |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Promyelocytic Leukemia