Childhood Acute Lymphoblastic Leukemia Treatment Protocol Moscow-Berlin 2015 (ALL-MB 2015)

Federal Research Institute of Pediatric Hematology, Oncology and Immunology4,000 enrolled

Overview

QUESTIONS AND OBJECTIVES OF ALL-MB 2015 STUDY 1. Will the new risk group stratification (especially of T-ALL) to improve overall and event-free survival? 2. Will the new protocol is effective and feasible in patients older than 15 years, and especially in young adults? 3. Whether the intermittent dexamethasone administration in induction will result in a decrease in toxicity and mortality without loss of efficacy? 4. Whether the methylprednisolone administration as basic glucocorticoids during induction, consolidation and maintenance therapy will lead to decrease of severe infections and early mortality rate, improve survival and therapy compliance in adolescents and young adults with B-precursor ALL? 5. Whether the administration of Bortezomib in patients with B-precursor ALL with initial WBC≥100,000/µl will improve treatment outcome? 6. Whether the administration of Idarubicin instead Daunorubicin in low-risk T-ALL patients and two-phase induction in intermediate-risk T-ALL patients will reduce relapse rate and improve survival?

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

4,000

Conditions

Childhood Acute Lymphoblastic Leukemia

Interventions

6 mg/m2, per os, in two divided doses per day q12 hours. 1-28 day (dose in the first few days is depending on the total tumor mass). From day 29 the dose of dexamethasone is reducing: days 29-31 - 3 mg/m2, days 32-34 - 1.5 mg/m2, days 35-36 - 0.75 mg/m2; then dexamethasone is discontinued completely.

Dexamethasone intermittentDRUG

6 mg/m2, per os, in two divided doses per day q12 hours. Days: 1-14 (dose in the first few days is depending on the total tumor mass) and 22-28; days 15-21 - pause. From day 29 the dose of dexamethasone is reducing: days 29-30 - 3 mg/m2, days 31-32 - 1.5 mg/m2, then dexamethasone is discontinued completely.

DexamethasoneDRUG

Induction: 6 mg/m2, per os, in two divided doses per day q12 hours. 1-28 day (dose in the first few days is depending on the total tumor mass). From day 29 the dose of dexamethasone is reducing: days 29-31 - 3 mg/m2, days 32-34 - 1.5 mg/m2, days 35-36 - 0.75 mg/m2; then dexamethasone is discontinued completely. Consolidation: 6 mg/m2 per os, in two divided doses per day q12 hours. Weeks 13-14 (days 85-98), weeks 21-22 (days 141-154), weeks 29-30 (days 197-210), weeks 37-38 (days 253-260), weeks 45-46 (days 309-316), weeks 53-54 (days 365-372). Maintenance therapy: 6 mg/m2, per os, in two divided doses per day q12 hours, for 10 days followed by quick discontinuation during 3 days. Weeks 61-62, 69-70, 77-78, 85-86, 93-94.

MethylprednisoloneDRUG

Induction: 60 mg/m2, per os, in two divided doses per day q12 hours. 1-28 day (dose in the first few days is depending on the total tumor mass). From day 29 the dose of dexamethasone is reducing: days 29-31 - 30 mg/m2, days 32-34 - 15 mg/m2, days 35-36 - 8 mg/m2; then methylprednisolone is discontinued completely. Consolidation: 60 mg/m2 per os, in two divided doses per day q12 hours. Weeks 13-14 (days 85-98), weeks 21-22 (days 141-154), weeks 29-30 (days 197-210), weeks 37-38 (days 253-260), weeks 45-46 (days 309-316), weeks 53-54 (days 365-372). Maintenance therapy: 60 mg/m2, per os, in two divided doses per day q12 hours, for 10 days followed by quick discontinuation during 3 days. Weeks 61-62, 69-70, 77-78, 85-86, 93-94.

DaunorubicinDRUG

Induction: 45 mg/m2, intravenously, for 6 hours on days 8 and 22. Consolidation: 30 mg/m2, intravenously, for 6 hours on days 44, 65 (consolidation S1); 107, 121 (consolidation S2); and 163 (consolidation S3).

IdarubicinDRUG

Induction: 10 mg/m2, intravenously, for 6 hours on days 8 and 22. Consolidation: 8 mg/m2, intravenously, for 6 hours on days 44, 65 (consolidation S1); 107, 121 (consolidation S2); and 163 (consolidation S3).

BortezomibDRUG

1.3 mg/м2, intravenously, bolus injection. Days 85, 89, 92, 96 (consolidation S1); 141, 145, 148, 152 (consolidation S2) and 197, 201, 204, 208 (consolidation S3).

Second phase of inductionDRUG

Cyclophosphamide (1,000 mg/m2, intravenously, for 1 hour - days 43 and 71); Cytarabine (75 mg/m2/day, intravenously, bolus injection. Four blocks of 4 days each, days 46-48, 52-55, 59-62, and 66-69); 6-mercaptopurine (60 mg/m2/day, per os, days 43-71); Triple intrathecal therapy (days 52 and 66)

Standard induction therapyDRUG

Dexamethasone (6 mg/m2, p/o; 1-29 days); Daunorubicin (45 mg/m2, i.v.; day 8 and 22); Vincristine (1.5 mg/m2, i.v.; days 8, 15, 22, 29 and 36); Triple intrathecal therapy (Methotrexate/Cytarabine/Prednisone; days 0/1, 8, 15, 22, 29 and 36)

Standard consolidation therapyDRUG

Consolidation consists of 3 phases: S1, S2 and S3. Each phase is a 6-week therapy with 6-mercaptopurine (50 mg/m2 per day, daily, orally), methotrexate (30 мг/м2, i.m., weekly) and L-asparaginase (10 000 U/m2, i.m., weekly), followed by 2 weeks of re-induction with Vincristine (1.5 mg/m2, i.v., days 1 and 8 of reinduction) plus Dexamethasone (6 mg/m2, p/o, daily, for 10 days followed by quick discontinuation during 3 days). Daunorubicin (30 mg/м2, i.v., N2 during S1, N2 during S2 and N1 during S3). Triple intrathecal therapy (Methotrexate/Cytarabine/Prednisone) N12 (4 injections per each phase)

Eligibility

Sex: ALLMin age: 1 YearMax age: 50 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age at diagnosis at 1 to 50 years. * The start of induction therapy within a time interval of study recruitment phase. * The diagnosis of ALL is to be proved by the morphological, cytochemical, and immunological analysis of tumor cells in bone marrow (see "Diagnostics"). Patients with B-cell (Burkitt) ALL are excluded. * Informed consent of the patient parents (guardians) to be treated in one of the clinics included in this multicenter study. Exclusion Criteria: * ALL is a second malignancies; * The disease is a relapse of previously misdiagnosed and, therefore, inadequately treated ALL; * There is severe concomitant disease, which significantly impedes chemotherapy protocol (such as multiple malformations, heart diseases, metabolic disorders, etc.); * There is a lack of important data needed for the exact adherence to the cytostatic therapy according to a specific chemotherapy protocol (differential diagnosis of ALL-AML (acute myeloid leukemia) is not possible, stratification according to therapeutic group is not possible); * The patient was treated before for a long time with cytotoxic drugs; * There were treatment deviations not covered by the protocol and/or not due to side effects of treatment and/or complications of the disease

Locations (58)

prof. R.O.Eolyan Hematology Center

Yerevan, Armenia

COMPLETED

Republican Research and Practical Center of Radiation Medicine and Human Ecology

Homyel, Belarus

RECRUITING

Republic Research and Practical Center of Pediatric Oncology, Hematology and Immunology

Minsk, Belarus

RECRUITING

Mogilev Regional Children's Hospital

Mogilev, Belarus