Childhood Acute Lymphoblastic Leukemia
Conditions
Keywords
Acute lymphoblastic leukemia, children, adolescents, L-asparaginase, methotrexate
Brief summary
QUESTIONS AND OBJECTIVES OF ALL-MB-2008 STUDY 1. Whether the early PEG-asparaginase in induction will lead to the earlier achievement of remission, improvement of days 8 and 15 responses leading to an earlier reconstitution of bone marrow and immunocompetence, decrease of severe infections and early mortality rate? 2. Whether the use of PEG-asparaginase in induction will allow to avoid the anthracyclines in standard risk group patients and to reduce treatment myelotoxicity? 3. Whether the administration of 9 doses of PEG-asparaginase 1,000 U/m2 instead of 18 doses of E.coli L-asparaginase 5,000 U/m2 in standard risk patients will improve treatment outcome? 4. Whether the administrations of high dose methotrexate (2 g/m2 in 24 hours) during 1-st consolidation in intermediate risk patients will result in decrease of central nervous system relapse incidence and improvement of event-free and overall survival? Whether the increase of 6-mercaptopurine starting dose up to 50 mg/m2 in 1-st consolidation phase (instead of 25 mg/m2) will decrease in relapse risk, but would not be accompanied with enhanced toxicity? 5. Is it possible to completely avoid the cranial irradiation in intermediate risk patients? In some subgroup of intermediate risk patients? Is it enough to control neuroleukemia in these patients to introduce additional TIT in the consolidation phase of treatment? How will change the possible late effects in these patients according to the third arm of randomization? 6. Will the new risk group stratification to improve overall and event-free survival?
Interventions
DRUGPEG-L-asparaginase ind
1,000 U/m2 on day 3 of induction therapy, intravenously, in 200 ml of saline, during 1 hour
DRUGPEG-L-asparaginase cons
1,000 U/m2 intravenously, in 200 ml of saline, during 1 hour, 24 hours after methotrexate on weeks 7, 9, and 11 - days 44, 58, and 72 (phase S1), weeks 15, 17, and 19 - days 100, 114, 128 (phase S2), weeks 23, 25, and 27 - days 156, 170, 184 (phase S3).
DRUGE.coli L-asparaginase
E.coli L-asparaginase (asparaginase medac) 5,000 U/m2 intramuscularly weekly, 24 hours after methotrexate dose, from week 7 to week 12 - days 44, 51, 58. 65, 72, 79 (phase S1), from week 15 to week 20 - days 100, 107, 114, 121, 128, 135 (phase S2), from week 23 to week 28 - days 156, 163, 170, 177, 184, 191 (phase S3).
2,000 mg/m2 per 24 hours is given at days 43, 57, and 71 (weeks 7, 9, and 11). 1/5 of the total dose is given as slow intravenous bolus over 3-5 minutes. 4/5 of the total dose of methotrexate is injected as continuous 24 hours infusion.
DRUGLow-dose Methotrexate
30 mg/м2 is given intramuscularly 1 time weekly - days 43, 50, 57, 64, 71, and 78 (weeks 7, 8, 9, 10, 11, and 12).
Intrathecal injection of 3 drugs is additionally given three times during phase S-2 (weeks 15, 17, and 19 - days 99, 113, and 127), and three times during phase S-3 (weeks 23, 25, and 27 - days 155, 169, and 183).
RADIATIONCranial irradiation
12 Gy cranial irradiation is conducted at weeks 31-32 of the Protocol in patients \>3 years of age
DRUGDaunorubicin
Daunorubicin at a dose of 45 mg/m2 i.v. for 6 hours on day 8 of induction therapy
Sponsors
Federal Research Institute of Pediatric Hematology, Oncology and Immunology
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
1. Age at diagnosis at 1 to 18 years. 2. The start of induction therapy within a time interval of study recruitment phase. 3. The diagnosis of ALL is to be proved by the morphological, cytochemical, and immunological analysis of tumor cells in bone marrow. 4. Informed consent of the parents (guardians) of the patient to be treated in one of the clinics included in this multicenter study.
Exclusion criteria
1. ALL is a second malignant tumor; 2. The disease is a relapse of previously misdiagnosed and, therefore, inadequately treated ALL; 3. There is severe concomitant disease, which significantly impedes chemotherapy protocol (such as multiple malformations, heart diseases, metabolic disorders, etc.); 4. There is a lack of important basic data needed for the exact adherence to the cytostatic therapy according to a specific protocol of chemotherapy (differential diagnosis of acute lymphoblastic/myeloid leukemia is not possible, stratification according to risk group is not possible); 5. The patient was treated before for a long time with cytotoxic drugs; 6. There were deviations in the treatment not covered by the protocol and/or not due to side effects of treatment and/or complications of the disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Event-free survival | 3 years, 5 years and 10 years after study start |
| overall survival | 3 years, 5 years and 10 years after study start |
| cumulative incidence of relapse | 3 years, 5 years and 10 years after study start |
Secondary
| Measure | Time frame |
|---|---|
| early death rate | 3 years, 5 years and 10 years after study start |
| remission death rate | 3 years, 5 years and 10 years after study start |
Countries
Belarus, Russia, Uzbekistan
Outcome results
None listed