Childhood Acute Lymphoblastic Leukemia Treatment Protocol Moscow-Berlin 2008 (ALL-MB 2008)

Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Status: Unknown

Conditions: Childhood Acute Lymphoblastic Leukemia

Treatments: Drug: High-dose Methotrexate; Drug: Daunorubicin; Drug: PEG-L-asparaginase cons; Drug: Triple intrathecal therapy; Drug: PEG-L-asparaginase ind; Drug: Low-dose Methotrexate; Radiation: Cranial irradiation; Drug: E.coli L-asparaginase

Study type: Interventional

Funder types: Other

Identifiers

NCT01953770

ALL-MB 2008

Details and patient eligibility

About

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?

Enrollment: 3,000 estimated patients

Sex: All

Ages: 1 to 18 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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3,000 participants in 9 patient groups

Cranial irradiation

Active Comparator group

Description:

Consolidation therapy with cranial irradiation in intermediate risk group patients

Treatment:

Radiation: Cranial irradiation

Additional TIT

Experimental group

Description:

Consolidation therapy with additional triple intrathecal therapy (N6) and without cranial irradiation in intermediate risk group patients

Treatment:

Drug: Triple intrathecal therapy

MTX 2,000 mg/m2

Experimental group

Description:

Consolidation therapy with High-dose Methotrexate 2,000 mg/m2/24 h i.v. biweekly in intermediate risk group patients

Treatment:

Drug: High-dose Methotrexate

MTX 30 mg/m2

Active Comparator group

Description:

Consolidation therapy with Low-dose Methotrexate 30 mg/m2 i.m. weekly in intermediate risk group patients

Treatment:

Drug: Low-dose Methotrexate

PEG-asp 1,000 U/m2

Experimental group

Description:

Consolidation therapy with PEG-L-asparaginase cons 1,000 U/m2 biweekly in standard risk group patients

Treatment:

Drug: PEG-L-asparaginase cons

L-asp 5,000 U/m2

Active Comparator group

Description:

Consolidation therapy with E.coli L-asparaginase 5,000 U/m2 weekly in standard risk group patients

Treatment:

Drug: E.coli L-asparaginase

PEG-DNR+

Active Comparator group

Description:

Induction therapy without PEG-L-asparaginase and with Daunorubicin 45 mg/m2 in standard and intermediate risk group patients

Treatment:

Drug: Daunorubicin

PEG+DNR+

Experimental group

Description:

Induction therapy with PEG-L-asparaginase ind (1,000 U/m2 on day 3 of therapy)and daunorubicin 45 mg/m2 in standard and intermediate risk group patients

Treatment:

Drug: PEG-L-asparaginase ind

Drug: Daunorubicin

PEG+DNR-

Experimental group

Description:

Induction therapy with PEG-L-asparaginase ind (1,000 U/m2 on day 3 of therapy) without daunorubicin on day 8 in standard risk group patients

Treatment:

Drug: PEG-L-asparaginase ind