Childhood Acute Lymphoblastic Leukemia Treatment Protocol Moscow-Berlin 2008

NCT ID: NCT01953770

Last Updated: 2020-02-05

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 3000 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-02-29
• Study Completion Date: 2020-07-31

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?

Conditions

Childhood Acute Lymphoblastic Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cranial irradiation

Consolidation therapy with cranial irradiation in intermediate risk group patients

Group Type: ACTIVE_COMPARATOR

Cranial irradiation

Intervention Type: RADIATION

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

Additional TIT

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

Group Type: EXPERIMENTAL

Triple intrathecal therapy

Intervention Type: DRUG

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).

MTX 2,000 mg/m2

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

Group Type: EXPERIMENTAL

High-dose Methotrexate

Intervention Type: DRUG

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.

MTX 30 mg/m2

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

Group Type: ACTIVE_COMPARATOR

Low-dose Methotrexate

Intervention Type: DRUG

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).

PEG-asp 1,000 U/m2

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

Group Type: EXPERIMENTAL

PEG-L-asparaginase cons

Intervention Type: DRUG

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).

L-asp 5,000 U/m2

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

Group Type: ACTIVE_COMPARATOR

E.coli L-asparaginase

Intervention Type: DRUG

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).

PEG-DNR+

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

Group Type: ACTIVE_COMPARATOR

Daunorubicin

Intervention Type: DRUG

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

PEG+DNR+

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

Group Type: EXPERIMENTAL

PEG-L-asparaginase ind

Intervention Type: DRUG

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

Daunorubicin

Intervention Type: DRUG

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

PEG+DNR-

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

Group Type: EXPERIMENTAL

PEG-L-asparaginase ind

Intervention Type: DRUG

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

Interventions

PEG-L-asparaginase ind

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

Intervention Type: 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).

Intervention Type: 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).

Intervention Type: 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.

Intervention Type: 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).

Intervention Type: 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).

Intervention Type: DRUG

Cranial irradiation

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

Intervention Type: RADIATION

Daunorubicin

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

Intervention Type: DRUG

Other Intervention Names

Asparaginase Medac; Methotrexate/Cytarabine/Prednisone i.th.

Eligibility Criteria

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

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Federal Research Institute of Pediatric Hematology, Oncology and Immunology

OTHER

Sponsor Role: lead

Responsible Party

Karachunskiy Alexander

Deputy director of Research Institute of Pediatric Hematology, Oncology and Immunology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Alexander I. Karachunskiy, Professor

Role: PRINCIPAL_INVESTIGATOR

Research Institute of Pediatric Hematology, Oncology and Immunology

Locations

Republican Research and Practical Center of Radiation Medicine

Homyel, , Belarus

Republic Research and Practical Center of Pediatric Oncology and Hematology

Minsk, , Belarus

Mogilev Regional Children's Hospital

Mogilev, , Belarus

Arkhangelsk Regional Children's Hospital

Arkhangelsk, , Russia

Regional Children's Hospital

Astrakhan, , Russia

Moscow Regional Cancer Dispensary

Balashikha, , Russia

Amur Regional Children's Hospital

Blagoveshchensk, , Russia

Chelyabinsk Regional Children's Clinical Hospital

Chelyabinsk, , Russia

Irkutsk Regional Children Clinical Hospital

Irkutsk, , Russia

Regional Clinical Hospital

Ivanovo, , Russia

Regional Children's Clinical Hospital

Khabarovsk, , Russia

Kirov Research Institute of Hematology and Blood Transfusion

Kirov, , Russia

Regional Children's Hospital

Krasnodar, , Russia

Krasnoyarsk Territorial Clinical Children Hospital

Krasnoyarsk, , Russia

Regional Children's Hospital

Kursk, , Russia

Republic Children's Clinical Hospital

Makhachkala, , Russia

Morozov Children's Clinical Hospital

Moscow, , Russia

Research Institute of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogachev

Moscow, , Russia

Russian Children's Clinic Hospital

Moscow, , Russia

Republic Children's Clinical Hospital

Nal'chik, , Russia

District Children's Clinic Hospital

Nizhnevartovsk, , Russia

Regional Children's Clinic Hospital

Nizhny Novgorod, , Russia

Municipal Children's Clinic Hospital №4

Novokuznetsk, , Russia

Novosibirsk Central District Hospital

Novosibirsk, , Russia

Regional Clinical Oncology Dispensary

Orenburg, , Russia

Perm Regional Children's Clinic Hospital

Perm, , Russia

Regional Children's Hospital

Rostov-on-Don, , Russia

Rostov Research Institute of Oncology

Rostov-on-Don, , Russia

N. Dmitrieva Ryazan Regional Children's Hospital

Ryazan, , Russia

Children's Municipal Hospital №1

Saint Petersburg, , Russia

Municipal Hospital №31

Saint Petersburg, , Russia

R. Gorbacheva Research Institute of Pediatric Hematology and Transfusiology; Pavlov State Medical University of Saint-Petersburg

Saint Petersburg, , Russia

Children's Municipal Clinical Hospital №1

Samara, , Russia

Profpathology and Hematology Clinic; Saratov State Medical University

Saratov, , Russia

Regional Children's Clinical Hospital

Stavropol, , Russia

Surgut Central District Clinical Hospital

Surgut, , Russia

Tomsk Regional Clinical Hospital

Tomsk, , Russia

Tula Regional Children's Hospital

Tula, , Russia

Republic Children's Clinical Hospital

Ulan-Ude, , Russia

Ulyanovsk Regional Children's Clinical Hospital

Ulyanovsk, , Russia

Municipal Children's City Hospital, Territorial Children's Hematological Center

Vladivostok, , Russia

Voronezh Regional Children Clinical Hospital №1

Voronezh, , Russia

Republic Hospital №1 - National Medicine Centre

Yakutsk, , Russia

Regional Children's Clinical Hospital

Yaroslavl, , Russia

Regional Children's Clinical Hospital № 1

Yekaterinburg, , Russia

Research Institute of Hematology and Blood Transfusion

Tashkent, , Uzbekistan

Countries

Belarus; Russia; Uzbekistan

Related Links

http://www.mbstudy.net

Study web-site

Other Identifiers

ALL-MB 2008

Identifier Type: -

Identifier Source: org_study_id