LAL-AR-N-2005:Study Treatment for Children High Risk Acute Lymphoblastic Leukemia

Study Overview
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Brief Summary
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The study objective is to improve the global results obtained with LAL-AR-93 study, reaching an event free survival between 60-70%. Identify patients with bad prognosis, with minimal residual disease,who can benefit of allogenic bone marrow transplantation

Detailed Description
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INDUCTION TREATMENT Systemic chemotherapy: PREDNISOLONE 60 mg/m2 /day, oral or i.v. x 21 days (1 to 22) 30 mg/m2 /day, oral or i.v. x 7 days (23 to 29) DAUNORUBICIN 30 mg/m2 , i.v. days 1,8,15 and 22 VINCRISTINE 1,5 mg/m2, i.v. days 1,8,15 and 22 L-ASPARAGINASE 10.000U/m2 i.m or i.v day 9,11,13,16,18,20,23,25 and 27 CYCLOPHOSPHAMIDE 500 mg/m2 i.v. days 1,2 and 29 Intrathecal chemotherapy: Days 1 and 22 according age: Age <1 years 1-3 years >3 years Methotrexate (MTX), mg 5 8 12 Ara-C, mg 16 20 30 Hydrocortisone,mg 10 10 20 Patients with <10% blasts in M.O (day 14), and in complete response on week 5 or 6, and without MDR, start consolidation-intensification phase. Patients with >10% blasts in MO day +14 or without CR after induction treatment, start consolidation-intensification phase and identifier a donor for a transplantation. CONSOLIDATION/INTENSIFICATION (C.I.) Two sequential cycles, alternating bloc I and bloc II BLOC I DEXAMETHASONE 10 mg/m2/d vo. days 1 to 5 and 5 mg/m2/d vo. days 6 and 7 VINCRISTINE 1.5 mg/m2/d, i.v. days 1 and 8 METHOTREXATE 5 g/m2 24 hours infusion + AF, day 1 ARA-C 1 g/m2/12 h, i.v., days 5 and 6 MERCAPTOPURINE 100 mg/m2/d, oral, days 1 to 5 CYCLOPHOSPHAMIDE 500 mg/m2 i.v. el day +8 INTRATHECAL CHEMOTHERAPY day 1. BLOC II DEXAMETHASONE 10 mg/m2/d, v o. days 1-5 and 5 mg/m2/d, v o. days 6 and 7 VINCRISTINE 1.5 mg/m2/d, days 1 and 8 METHOTREXATE 5 g/m2 24 h infusion + AF, day 1 ARA-C 1 g/m2 i.v/12 h, days 5 and 6 DAUNORUBICINE 30 mg/m2 i.v.day 1 L-ASPARAGINASE 20.000 u/m2/d, i.m. or i.v. day 7 INTRATHECAL CHEMOTHERAPY day 1 Patients with CR and MRD negative, follow chemotherapy. Patients with MDR >0.01% after second cycle or considered previously MRD are candidates to allogenic transplantation after second cycle. REINDUCTION/INTENSIFICATION TREATMENT (R.I.) PREDNISOLONE 60 mg/m2/d, oral x 14 days (1-14) 30 mg/m2/d, oral x 7 days (15-22) VINCRISTINE 1.5 mg/m2, i.v. x 2 days 1 and 8 DAUNORUBICINE 30 mg/m2 i.v x 2 , days 1 and 8 CYCLOPHOSPHAMIDE 500 mg/m2 I.V. day 15 ----------------------------------------- METHOTREXATE 3 g/m2 /24 h infusion + AF day 29 MERCAPTOPURINE 50 mg/m2/d, oral, days 29-35 and 43-50 ARA-C 1 g/m2/12 h., i.v., days 43 and 44 INTRATHECAL CHEMOTHERAPY , days 1, 15, 29 and 43 MAINTENANACE TREATMENT (M1) Six cycles of: MERCAPTOPURINE 50 mg/m2/d, oral x 21 days (1-21) METHOTREXATE 20 mg/m2/d, i.m. /week x 3 (1,7,14) PREDNISOLONE 60 mg/m2/d, oral x 7 days (22-28) VINCRISTINE 1.5 mg/m2 i.v.day 22 ASPARAGINASE 20.000 u/m2 i.m. day 22 INTRATHECAL CHEMOTHERAPY day 22 MAINTENANCE TREATMENT (M2) Diary mercaptopurine and weekly methotrexate at previous doses, until complete 24 months.

Official Title
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LAL-AR-N-2005: Study Treatment for Children High Risk Acute Lymphoblastic Leukemia

Conditions
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Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Drug: Prednisolone
* Drug: Daunorubicin
* Drug: Vincristine
* Drug: L-Asparaginase
* Drug: Cyclophosphamide
* Drug: Methotrexate
* Drug: Cytosine Arabinoside


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: High risk children with acute lymphoblastic leukemia Exclusion Criteria: Mature B-ALL (FABL3) Mixed forms of ALL Patients with coronary disorders, valvular or hypertensive cardiopathy Patients with chronic liver disorders Chronic pulmonary disorders Renal insufficiency Neurologic disfunctions ECOG 3 and 4

Ages Eligible for Study
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Maximum Age: 16 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: Prednisolone|Induction: 60 mg/m2/day, oral or i.v x 21 days and 30 mg/m2/day oral or iv x 7 days Reinduction-Intensification Treatment: 60 mg/m2/d x 14 days and 30 mg/m2/day oral x 7 days|
|Drug: Daunorubicin|Induction: 30 mg/m2, i.v, days 1, 8, 15, 22 Consolidation (Bloc II)30 mg/m2, i.v, day 1|
|Drug: Vincristine|Induction: 1,5 mg/m2 iv, days 1, 8, 15, 22 Consolidation (Bloc I):1,5 mg/m2 iv, days 1, 8 Consolidation (Bloc II):1,5 mg/m2 iv, days 1, 8 Reinduction: 1,5 mg/m2 iv, days 1, 8 Maintenance:1,5 mg/m2 iv, day 22|
|Drug: L-Asparaginase|Induction: 10.000 U/m2 im or iv, days 9,11,13,16,18,20,23,25,27 Consolidation (Bloc II): 20.000 U/m2 im or iv, day 7 Maintenance: 20.000 U/m2 im or iv, day 22|
|Drug: Cyclophosphamide|Induction: 500 mg/m2 iv, days 1, 2, 29 Consolidation (Bloc I): 500 mg/m2 iv, day 8 Reinduction:500 mg/m2 iv, day 15|
|Drug: Methotrexate|Consolidation (Bloc I): 5 g/m2 24 hours infusion Consolidation (Bloc II): 5 g/m2 24 hours infusion Reinduction: 3 g/m2 24 hours infusion Maintenance: 20 mg/m2/d, IM/week x 3 (1, 7, 14)|
|Drug: Cytosine Arabinoside|Consolidation (Bloc I): 1 g/m2/12 h iv, days 5, 6 Consolidation (Bloc II): 1 g/m2/12 h iv, days 5, 6 Reinduction: 1 g/m2/12 h iv, days 43, 44|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To improve the global results obtained in PETHEMA LAL-AR-93 study in terms of events free time |  | 2 years | 

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