Clinical trial NCT01953770: Childhood Acute Lymphoblastic Leukemia Treatment Protocol Moscow-Berlin 2008
Official title: Moscow-Berlin 2008 Multicenter Randomised Study for Treatment of Acute Lymphoblastic Leukemia in Children and Adolescents
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Childhood Acute Lymphoblastic Leukemia
Keywords: Acute lymphoblastic leukemia, children, adolescents, L-asparaginase, methotrexate
Lead sponsor: Federal Research Institute of Pediatric Hematology, Oncology and Immunology
Sponsor class: OTHER
First posted: 2013-10-01
Enrollment: 3000
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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?


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

Primary outcomes:
measure: Event-free survival
timeFrame: 3 years, 5 years and 10 years after study start
measure: overall survival
timeFrame: 3 years, 5 years and 10 years after study start
measure: cumulative incidence of relapse
timeFrame: 3 years, 5 years and 10 years after study start
Secondary outcomes:
measure: early death rate
timeFrame: 3 years, 5 years and 10 years after study start
measure: remission death rate
timeFrame: 3 years, 5 years and 10 years after study start
Other outcomes:
Locations:
city: Gomel
country: Belarus
facility: Republican Research and Practical Center of Radiation Medicine
city: Minsk
country: Belarus
facility: Republic Research and Practical Center of Pediatric Oncology and Hematology
city: Mogilev
country: Belarus
facility: Mogilev Regional Children's Hospital
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk Regional Children's Hospital
city: Astrakhan
country: Russian Federation
facility: Regional Children's Hospital
city: Balashikha
country: Russian Federation
facility: Moscow Regional Cancer Dispensary
city: Blagoveshchensk
country: Russian Federation
facility: Amur Regional Children's Hospital
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinsk Regional Children's Clinical Hospital
city: Irkutsk
country: Russian Federation
facility: Irkutsk Regional Children Clinical Hospital
city: Ivanovo
country: Russian Federation
facility: Regional Clinical Hospital
city: Khabarovsk
country: Russian Federation
facility: Regional Children's Clinical Hospital
city: Kirov
country: Russian Federation
facility: Kirov Research Institute of Hematology and Blood Transfusion
city: Krasnodar
country: Russian Federation
facility: Regional Children's Hospital
city: Krasnoyarsk
country: Russian Federation
facility: Krasnoyarsk Territorial Clinical Children Hospital
city: Kursk
country: Russian Federation
facility: Regional Children's Hospital
city: Makhachkala
country: Russian Federation
facility: Republic Children's Clinical Hospital
city: Moscow
country: Russian Federation
facility: Morozov Children's Clinical Hospital
city: Moscow
country: Russian Federation
facility: Research Institute of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogachev
city: Moscow
country: Russian Federation
facility: Russian Children's Clinic Hospital
city: Nalchik
country: Russian Federation
facility: Republic Children's Clinical Hospital
city: Nizhnevartovsk
country: Russian Federation
facility: District Children's Clinic Hospital
city: Nizhny Novgorod
country: Russian Federation
facility: Regional Children's Clinic Hospital
city: Novokuznetsk
country: Russian Federation
facility: Municipal Children's Clinic Hospital №4
city: Novosibirsk
country: Russian Federation
facility: Novosibirsk Central District Hospital
city: Orenburg
country: Russian Federation
facility: Regional Clinical Oncology Dispensary
city: Perm
country: Russian Federation
facility: Perm Regional Children's Clinic Hospital
city: Rostov-on-Don
country: Russian Federation
facility: Regional Children's Hospital
city: Rostov-on-Don
country: Russian Federation
facility: Rostov Research Institute of Oncology
city: Ryazan
country: Russian Federation
facility: N. Dmitrieva Ryazan Regional Children's Hospital
city: Saint Petersburg
country: Russian Federation
facility: Children's Municipal Hospital №1
city: Saint Petersburg
country: Russian Federation
facility: Municipal Hospital №31
city: Saint Petersburg
country: Russian Federation
facility: R. Gorbacheva Research Institute of Pediatric Hematology and Transfusiology; Pavlov State Medical University of Saint-Petersburg
city: Samara
country: Russian Federation
facility: Children's Municipal Clinical Hospital №1
city: Saratov
country: Russian Federation
facility: Profpathology and Hematology Clinic; Saratov State Medical University
city: Stavropol
country: Russian Federation
facility: Regional Children's Clinical Hospital
city: Surgut
country: Russian Federation
facility: Surgut Central District Clinical Hospital
city: Tomsk
country: Russian Federation
facility: Tomsk Regional Clinical Hospital
city: Tula
country: Russian Federation
facility: Tula Regional Children's Hospital
city: Ulan-Ude
country: Russian Federation
facility: Republic Children's Clinical Hospital
city: Ulyanovsk
country: Russian Federation
facility: Ulyanovsk Regional Children's Clinical Hospital
city: Vladivostok
country: Russian Federation
facility: Municipal Children's City Hospital, Territorial Children's Hematological Center
city: Voronezh
country: Russian Federation
facility: Voronezh Regional Children Clinical Hospital №1
city: Yakutsk
country: Russian Federation
facility: Republic Hospital №1 - National Medicine Centre
city: Yaroslavl
country: Russian Federation
facility: Regional Children's Clinical Hospital
city: Yekaterinburg
country: Russian Federation
facility: Regional Children's Clinical Hospital № 1
city: Tashkent
country: Uzbekistan
facility: Research Institute of Hematology and Blood Transfusion
Study officials:
affiliation: Research Institute of Pediatric Hematology, Oncology and Immunology
name: Alexander I. Karachunskiy, Professor
role: PRINCIPAL_INVESTIGATOR
References: