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

Primary Purpose

Childhood Acute Lymphoblastic Leukemia

Status
Unknown status
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
PEG-L-asparaginase ind
PEG-L-asparaginase cons
E.coli L-asparaginase
High-dose Methotrexate
Low-dose Methotrexate
Triple intrathecal therapy
Cranial irradiation
Daunorubicin
Sponsored by
Federal Research Institute of Pediatric Hematology, Oncology and Immunology
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Childhood Acute Lymphoblastic Leukemia focused on measuring Acute lymphoblastic leukemia, children, adolescents, L-asparaginase, methotrexate

Eligibility Criteria

1 Year - 18 Years (Child, Adult)All SexesDoes not accept 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

Sites / Locations

  • Republican Research and Practical Center of Radiation Medicine
  • Republic Research and Practical Center of Pediatric Oncology and Hematology
  • Mogilev Regional Children's Hospital
  • Arkhangelsk Regional Children's Hospital
  • Regional Children's Hospital
  • Moscow Regional Cancer Dispensary
  • Amur Regional Children's Hospital
  • Chelyabinsk Regional Children's Clinical Hospital
  • Irkutsk Regional Children Clinical Hospital
  • Regional Clinical Hospital
  • Regional Children's Clinical Hospital
  • Kirov Research Institute of Hematology and Blood Transfusion
  • Regional Children's Hospital
  • Krasnoyarsk Territorial Clinical Children Hospital
  • Regional Children's Hospital
  • Republic Children's Clinical Hospital
  • Morozov Children's Clinical Hospital
  • Research Institute of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogachev
  • Russian Children's Clinic Hospital
  • Republic Children's Clinical Hospital
  • District Children's Clinic Hospital
  • Regional Children's Clinic Hospital
  • Municipal Children's Clinic Hospital №4
  • Novosibirsk Central District Hospital
  • Regional Clinical Oncology Dispensary
  • Perm Regional Children's Clinic Hospital
  • Regional Children's Hospital
  • Rostov Research Institute of Oncology
  • N. Dmitrieva Ryazan Regional Children's Hospital
  • Children's Municipal Hospital №1
  • Municipal Hospital №31
  • R. Gorbacheva Research Institute of Pediatric Hematology and Transfusiology; Pavlov State Medical University of Saint-Petersburg
  • Children's Municipal Clinical Hospital №1
  • Profpathology and Hematology Clinic; Saratov State Medical University
  • Regional Children's Clinical Hospital
  • Surgut Central District Clinical Hospital
  • Tomsk Regional Clinical Hospital
  • Tula Regional Children's Hospital
  • Republic Children's Clinical Hospital
  • Ulyanovsk Regional Children's Clinical Hospital
  • Municipal Children's City Hospital, Territorial Children's Hematological Center
  • Voronezh Regional Children Clinical Hospital №1
  • Republic Hospital №1 - National Medicine Centre
  • Regional Children's Clinical Hospital
  • Regional Children's Clinical Hospital № 1
  • Research Institute of Hematology and Blood Transfusion

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm Type

Active Comparator

Experimental

Experimental

Active Comparator

Experimental

Active Comparator

Active Comparator

Experimental

Experimental

Arm Label

Cranial irradiation

Additional TIT

MTX 2,000 mg/m2

MTX 30 mg/m2

PEG-asp 1,000 U/m2

L-asp 5,000 U/m2

PEG-DNR+

PEG+DNR+

PEG+DNR-

Arm Description

Consolidation therapy with cranial irradiation in intermediate risk group patients

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

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

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

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

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

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

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

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

Outcomes

Primary Outcome Measures

Event-free survival
overall survival
cumulative incidence of relapse

Secondary Outcome Measures

early death rate
remission death rate

Full Information

First Posted
September 26, 2013
Last Updated
February 4, 2020
Sponsor
Federal Research Institute of Pediatric Hematology, Oncology and Immunology
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1. Study Identification

Unique Protocol Identification Number
NCT01953770
Brief Title
Childhood Acute Lymphoblastic Leukemia Treatment Protocol Moscow-Berlin 2008
Acronym
ALL-MB 2008
Official Title
Moscow-Berlin 2008 Multicenter Randomised Study for Treatment of Acute Lymphoblastic Leukemia in Children and Adolescents
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Unknown status
Study Start Date
February 2008 (Actual)
Primary Completion Date
January 2015 (Actual)
Study Completion Date
July 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Federal Research Institute of Pediatric Hematology, Oncology and Immunology

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
QUESTIONS AND OBJECTIVES OF ALL-MB-2008 STUDY 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? Whether the use of PEG-asparaginase in induction will allow to avoid the anthracyclines in standard risk group patients and to reduce treatment myelotoxicity? 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? 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? 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? Will the new risk group stratification to improve overall and event-free survival?

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Childhood Acute Lymphoblastic Leukemia
Keywords
Acute lymphoblastic leukemia, children, adolescents, L-asparaginase, methotrexate

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
3000 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cranial irradiation
Arm Type
Active Comparator
Arm Description
Consolidation therapy with cranial irradiation in intermediate risk group patients
Arm Title
Additional TIT
Arm Type
Experimental
Arm Description
Consolidation therapy with additional triple intrathecal therapy (N6) and without cranial irradiation in intermediate risk group patients
Arm Title
MTX 2,000 mg/m2
Arm Type
Experimental
Arm Description
Consolidation therapy with High-dose Methotrexate 2,000 mg/m2/24 h i.v. biweekly in intermediate risk group patients
Arm Title
MTX 30 mg/m2
Arm Type
Active Comparator
Arm Description
Consolidation therapy with Low-dose Methotrexate 30 mg/m2 i.m. weekly in intermediate risk group patients
Arm Title
PEG-asp 1,000 U/m2
Arm Type
Experimental
Arm Description
Consolidation therapy with PEG-L-asparaginase cons 1,000 U/m2 biweekly in standard risk group patients
Arm Title
L-asp 5,000 U/m2
Arm Type
Active Comparator
Arm Description
Consolidation therapy with E.coli L-asparaginase 5,000 U/m2 weekly in standard risk group patients
Arm Title
PEG-DNR+
Arm Type
Active Comparator
Arm Description
Induction therapy without PEG-L-asparaginase and with Daunorubicin 45 mg/m2 in standard and intermediate risk group patients
Arm Title
PEG+DNR+
Arm Type
Experimental
Arm 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
Arm Title
PEG+DNR-
Arm Type
Experimental
Arm 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
Intervention Type
Drug
Intervention Name(s)
PEG-L-asparaginase ind
Intervention Description
1,000 U/m2 on day 3 of induction therapy, intravenously, in 200 ml of saline, during 1 hour
Intervention Type
Drug
Intervention Name(s)
PEG-L-asparaginase cons
Intervention Description
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
Intervention Name(s)
E.coli L-asparaginase
Other Intervention Name(s)
Asparaginase Medac
Intervention Description
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
Intervention Name(s)
High-dose Methotrexate
Intervention Description
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
Intervention Name(s)
Low-dose Methotrexate
Intervention Description
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
Intervention Name(s)
Triple intrathecal therapy
Other Intervention Name(s)
Methotrexate/Cytarabine/Prednisone i.th.
Intervention Description
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
Radiation
Intervention Name(s)
Cranial irradiation
Intervention Description
12 Gy cranial irradiation is conducted at weeks 31-32 of the Protocol in patients >3 years of age
Intervention Type
Drug
Intervention Name(s)
Daunorubicin
Intervention Description
Daunorubicin at a dose of 45 mg/m2 i.v. for 6 hours on day 8 of induction therapy
Primary Outcome Measure Information:
Title
Event-free survival
Time Frame
3 years, 5 years and 10 years after study start
Title
overall survival
Time Frame
3 years, 5 years and 10 years after study start
Title
cumulative incidence of relapse
Time Frame
3 years, 5 years and 10 years after study start
Secondary Outcome Measure Information:
Title
early death rate
Time Frame
3 years, 5 years and 10 years after study start
Title
remission death rate
Time Frame
3 years, 5 years and 10 years after study start

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age at diagnosis at 1 to 18 years. The start of induction therapy within a time interval of study recruitment phase. The diagnosis of ALL is to be proved by the morphological, cytochemical, and immunological analysis of tumor cells in bone marrow. Informed consent of the parents (guardians) of the patient to be treated in one of the clinics included in this multicenter study. Exclusion Criteria: ALL is a second malignant tumor; The disease is a relapse of previously misdiagnosed and, therefore, inadequately treated ALL; There is severe concomitant disease, which significantly impedes chemotherapy protocol (such as multiple malformations, heart diseases, metabolic disorders, etc.); 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); The patient was treated before for a long time with cytotoxic drugs; 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alexander I. Karachunskiy, Professor
Organizational Affiliation
Research Institute of Pediatric Hematology, Oncology and Immunology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Republican Research and Practical Center of Radiation Medicine
City
Gomel
Country
Belarus
Facility Name
Republic Research and Practical Center of Pediatric Oncology and Hematology
City
Minsk
Country
Belarus
Facility Name
Mogilev Regional Children's Hospital
City
Mogilev
Country
Belarus
Facility Name
Arkhangelsk Regional Children's Hospital
City
Arkhangelsk
Country
Russian Federation
Facility Name
Regional Children's Hospital
City
Astrakhan
Country
Russian Federation
Facility Name
Moscow Regional Cancer Dispensary
City
Balashikha
Country
Russian Federation
Facility Name
Amur Regional Children's Hospital
City
Blagoveshchensk
Country
Russian Federation
Facility Name
Chelyabinsk Regional Children's Clinical Hospital
City
Chelyabinsk
Country
Russian Federation
Facility Name
Irkutsk Regional Children Clinical Hospital
City
Irkutsk
Country
Russian Federation
Facility Name
Regional Clinical Hospital
City
Ivanovo
Country
Russian Federation
Facility Name
Regional Children's Clinical Hospital
City
Khabarovsk
Country
Russian Federation
Facility Name
Kirov Research Institute of Hematology and Blood Transfusion
City
Kirov
Country
Russian Federation
Facility Name
Regional Children's Hospital
City
Krasnodar
Country
Russian Federation
Facility Name
Krasnoyarsk Territorial Clinical Children Hospital
City
Krasnoyarsk
Country
Russian Federation
Facility Name
Regional Children's Hospital
City
Kursk
Country
Russian Federation
Facility Name
Republic Children's Clinical Hospital
City
Makhachkala
Country
Russian Federation
Facility Name
Morozov Children's Clinical Hospital
City
Moscow
Country
Russian Federation
Facility Name
Research Institute of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogachev
City
Moscow
Country
Russian Federation
Facility Name
Russian Children's Clinic Hospital
City
Moscow
Country
Russian Federation
Facility Name
Republic Children's Clinical Hospital
City
Nalchik
Country
Russian Federation
Facility Name
District Children's Clinic Hospital
City
Nizhnevartovsk
Country
Russian Federation
Facility Name
Regional Children's Clinic Hospital
City
Nizhny Novgorod
Country
Russian Federation
Facility Name
Municipal Children's Clinic Hospital №4
City
Novokuznetsk
Country
Russian Federation
Facility Name
Novosibirsk Central District Hospital
City
Novosibirsk
Country
Russian Federation
Facility Name
Regional Clinical Oncology Dispensary
City
Orenburg
Country
Russian Federation
Facility Name
Perm Regional Children's Clinic Hospital
City
Perm
Country
Russian Federation
Facility Name
Regional Children's Hospital
City
Rostov-on-Don
Country
Russian Federation
Facility Name
Rostov Research Institute of Oncology
City
Rostov-on-Don
Country
Russian Federation
Facility Name
N. Dmitrieva Ryazan Regional Children's Hospital
City
Ryazan
Country
Russian Federation
Facility Name
Children's Municipal Hospital №1
City
Saint Petersburg
Country
Russian Federation
Facility Name
Municipal Hospital №31
City
Saint Petersburg
Country
Russian Federation
Facility Name
R. Gorbacheva Research Institute of Pediatric Hematology and Transfusiology; Pavlov State Medical University of Saint-Petersburg
City
Saint Petersburg
Country
Russian Federation
Facility Name
Children's Municipal Clinical Hospital №1
City
Samara
Country
Russian Federation
Facility Name
Profpathology and Hematology Clinic; Saratov State Medical University
City
Saratov
Country
Russian Federation
Facility Name
Regional Children's Clinical Hospital
City
Stavropol
Country
Russian Federation
Facility Name
Surgut Central District Clinical Hospital
City
Surgut
Country
Russian Federation
Facility Name
Tomsk Regional Clinical Hospital
City
Tomsk
Country
Russian Federation
Facility Name
Tula Regional Children's Hospital
City
Tula
Country
Russian Federation
Facility Name
Republic Children's Clinical Hospital
City
Ulan-Ude
Country
Russian Federation
Facility Name
Ulyanovsk Regional Children's Clinical Hospital
City
Ulyanovsk
Country
Russian Federation
Facility Name
Municipal Children's City Hospital, Territorial Children's Hematological Center
City
Vladivostok
Country
Russian Federation
Facility Name
Voronezh Regional Children Clinical Hospital №1
City
Voronezh
Country
Russian Federation
Facility Name
Republic Hospital №1 - National Medicine Centre
City
Yakutsk
Country
Russian Federation
Facility Name
Regional Children's Clinical Hospital
City
Yaroslavl
Country
Russian Federation
Facility Name
Regional Children's Clinical Hospital № 1
City
Yekaterinburg
Country
Russian Federation
Facility Name
Research Institute of Hematology and Blood Transfusion
City
Tashkent
Country
Uzbekistan

12. IPD Sharing Statement

Links:
URL
http://www.mbstudy.net
Description
Study web-site

Learn more about this trial

Childhood Acute Lymphoblastic Leukemia Treatment Protocol Moscow-Berlin 2008

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