Childhood Acute Lymphoblastic Leukemia Treatment Protocol Moscow-Berlin 2008

Not Applicable

• Conditions: Childhood Acute Lymphoblastic Leukemia
• Interventions: Drug: High-dose Methotrexate; Drug: Low-dose Methotrexate; Drug: PEG-L-asparaginase cons; Drug: PEG-L-asparaginase ind; Radiation: Cranial irradiation; Drug: Triple intrathecal therapy; Drug: E.coli L-asparaginase; Drug: Daunorubicin

• Registration Number: NCT01953770
• Lead Sponsor: Federal Research Institute of Pediatric Hematology, Oncology and Immunology

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?

Detailed Description

Not available

Study Timeline

• Study Start: 2008-02
• Study First Submitted: 2013-09-26
• Study First Submitted QC: 2013-09-26
• Study First Posted: 2013-10-01
• Primary Completion: 2015-01
• Status Verified: 2020-02
• Last Update Submitted: 2020-02-04
• Last Update Posted: 2020-02-05
• Study Completion: 2020-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 3000

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.

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
MTX 2,000 mg/m2	High-dose Methotrexate	Consolidation therapy with High-dose Methotrexate 2,000 mg/m2/24 h i.v. biweekly in intermediate risk group patients
MTX 30 mg/m2	Low-dose Methotrexate	Consolidation therapy with Low-dose Methotrexate 30 mg/m2 i.m. weekly in intermediate risk group patients
PEG-asp 1,000 U/m2	PEG-L-asparaginase cons	Consolidation therapy with PEG-L-asparaginase cons 1,000 U/m2 biweekly in standard risk group patients
PEG+DNR+	PEG-L-asparaginase ind	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
PEG+DNR-	PEG-L-asparaginase ind	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
Cranial irradiation	Cranial irradiation	Consolidation therapy with cranial irradiation in intermediate risk group patients
Additional TIT	Triple intrathecal therapy	Consolidation therapy with additional triple intrathecal therapy (N6) and without cranial irradiation in intermediate risk group patients
L-asp 5,000 U/m2	E.coli L-asparaginase	Consolidation therapy with E.coli L-asparaginase 5,000 U/m2 weekly in standard risk group patients
PEG-DNR+	Daunorubicin	Induction therapy without PEG-L-asparaginase and with Daunorubicin 45 mg/m2 in standard and intermediate risk group patients
PEG+DNR+	Daunorubicin	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

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (39)

Research Institute of Hematology and Blood Transfusion; 🇺🇿 Tashkent, Uzbekistan

Republic Hospital №1 - National Medicine Centre; 🇷🇺 Yakutsk, Russian Federation

Republican Research and Practical Center of Radiation Medicine; 🇧🇾 Gomel, Belarus

Republic Research and Practical Center of Pediatric Oncology and Hematology; 🇧🇾 Minsk, Belarus

Regional Children's Hospital; 🇷🇺 Rostov-on-Don, Russian Federation

Chelyabinsk Regional Children's Clinical Hospital; 🇷🇺 Chelyabinsk, Russian Federation

Research Institute of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogachev; 🇷🇺 Moscow, Russian Federation

Mogilev Regional Children's Hospital; 🇧🇾 Mogilev, Belarus

Russian Children's Clinic Hospital; 🇷🇺 Moscow, Russian Federation

Regional Children's Clinic Hospital; 🇷🇺 Nizhny Novgorod, Russian Federation

Children's Municipal Hospital №1; 🇷🇺 Saint Petersburg, Russian Federation

Municipal Hospital №31; 🇷🇺 Saint Petersburg, Russian Federation

Regional Clinical Oncology Dispensary; 🇷🇺 Orenburg, Russian Federation

District Children's Clinic Hospital; 🇷🇺 Nizhnevartovsk, Russian Federation

Children's Municipal Clinical Hospital №1; 🇷🇺 Samara, Russian Federation

Tula Regional Children's Hospital; 🇷🇺 Tula, Russian Federation

Perm Regional Children's Clinic Hospital; 🇷🇺 Perm, Russian Federation

Surgut Central District Clinical Hospital; 🇷🇺 Surgut, Russian Federation

Rostov Research Institute of Oncology; 🇷🇺 Rostov-on-Don, Russian Federation

Profpathology and Hematology Clinic; Saratov State Medical University; 🇷🇺 Saratov, Russian Federation

R. Gorbacheva Research Institute of Pediatric Hematology and Transfusiology; Pavlov State Medical University of Saint-Petersburg; 🇷🇺 Saint Petersburg, Russian Federation

Ulyanovsk Regional Children's Clinical Hospital; 🇷🇺 Ulyanovsk, Russian Federation

Voronezh Regional Children Clinical Hospital №1; 🇷🇺 Voronezh, Russian Federation

Arkhangelsk Regional Children's Hospital; 🇷🇺 Arkhangelsk, Russian Federation

Moscow Regional Cancer Dispensary; 🇷🇺 Balashikha, Russian Federation

Amur Regional Children's Hospital; 🇷🇺 Blagoveshchensk, Russian Federation

Irkutsk Regional Children Clinical Hospital; 🇷🇺 Irkutsk, Russian Federation

Regional Clinical Hospital; 🇷🇺 Ivanovo, Russian Federation

Regional Children's Clinical Hospital; 🇷🇺 Yaroslavl, Russian Federation

Kirov Research Institute of Hematology and Blood Transfusion; 🇷🇺 Kirov, Russian Federation

Morozov Children's Clinical Hospital; 🇷🇺 Moscow, Russian Federation

Krasnoyarsk Territorial Clinical Children Hospital; 🇷🇺 Krasnoyarsk, Russian Federation

Republic Children's Clinical Hospital; 🇷🇺 Ulan-Ude, Russian Federation

N. Dmitrieva Ryazan Regional Children's Hospital; 🇷🇺 Ryazan, Russian Federation

Municipal Children's Clinic Hospital №4; 🇷🇺 Novokuznetsk, Russian Federation

Novosibirsk Central District Hospital; 🇷🇺 Novosibirsk, Russian Federation

Tomsk Regional Clinical Hospital; 🇷🇺 Tomsk, Russian Federation

Municipal Children's City Hospital, Territorial Children's Hematological Center; 🇷🇺 Vladivostok, Russian Federation

Regional Children's Clinical Hospital № 1; 🇷🇺 Yekaterinburg, Russian Federation