Childhood Acute Lymphoblastic Leukemia Treatment Protocol Moscow-Berlin 2008

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?

Conditions

• Childhood Acute Lymphoblastic Leukemia

Interventions

DRUG

PEG-L-asparaginase ind

1,000 U/m2 on day 3 of induction therapy, intravenously, in 200 ml of saline, during 1 hour

DRUG

PEG-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).

DRUG

E.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).

DRUG

High-dose Methotrexate

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.

DRUG

Low-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).

DRUG

Triple intrathecal therapy

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).

RADIATION

Cranial irradiation

12 Gy cranial irradiation is conducted at weeks 31-32 of the Protocol in patients \>3 years of age

DRUG

Daunorubicin

Daunorubicin at a dose of 45 mg/m2 i.v. for 6 hours on day 8 of induction therapy

Sponsors & Collaborators

• Federal Research Institute of Pediatric Hematology, Oncology and Immunology

  lead OTHER

Principal Investigators

• Alexander I. Karachunskiy, Professor · Research Institute of Pediatric Hematology, Oncology and Immunology

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

1 Year

Max Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2008-02-29

Primary Completion

2015-01-31

Completion

2020-07-31

Countries

• Belarus
• Russia
• Uzbekistan

Study Locations