Childhood Acute Lymphoblastic Leukemia Treatment Protocol Moscow-Berlin 2008

Childhood Acute Lymphoblastic Leukemia Clinical Trial

— ALL-MB 2008  

Official title:

Moscow-Berlin 2008 Multicenter Randomised Study for Treatment of Acute Lymphoblastic Leukemia in Children and Adolescents

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01953770
• Other study ID #: ALL-MB 2008
• Status: Active, not recruiting
• Phase: N/A
• Start date: February 2008
• Est. completion date: July 2020

Study information

• Verified date: February 2020
• Source: Federal Research Institute of Pediatric Hematology, Oncology and Immunology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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?

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 3000
• Est. completion date: July 2020
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Childhood Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• PEG-L-asparaginase ind
1,000 U/m2 on day 3 of induction therapy, intravenously, in 200 ml of saline, during 1 hour
• 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).
• 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).
• 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.
• Low-dose Methotrexate
30 mg/?2 is given intramuscularly 1 time weekly - days 43, 50, 57, 64, 71, and 78 (weeks 7, 8, 9, 10, 11, and 12).
• 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

Locations

Country	Name	City	State
Belarus	Republican Research and Practical Center of Radiation Medicine	Gomel
Belarus	Republic Research and Practical Center of Pediatric Oncology and Hematology	Minsk
Belarus	Mogilev Regional Children's Hospital	Mogilev
Russian Federation	Arkhangelsk Regional Children's Hospital	Arkhangelsk
Russian Federation	Regional Children's Hospital	Astrakhan
Russian Federation	Moscow Regional Cancer Dispensary	Balashikha
Russian Federation	Amur Regional Children's Hospital	Blagoveshchensk
Russian Federation	Chelyabinsk Regional Children's Clinical Hospital	Chelyabinsk
Russian Federation	Irkutsk Regional Children Clinical Hospital	Irkutsk
Russian Federation	Regional Clinical Hospital	Ivanovo
Russian Federation	Regional Children's Clinical Hospital	Khabarovsk
Russian Federation	Kirov Research Institute of Hematology and Blood Transfusion	Kirov
Russian Federation	Regional Children's Hospital	Krasnodar
Russian Federation	Krasnoyarsk Territorial Clinical Children Hospital	Krasnoyarsk
Russian Federation	Regional Children's Hospital	Kursk
Russian Federation	Republic Children's Clinical Hospital	Makhachkala
Russian Federation	Morozov Children's Clinical Hospital	Moscow
Russian Federation	Research Institute of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogachev	Moscow
Russian Federation	Russian Children's Clinic Hospital	Moscow
Russian Federation	Republic Children's Clinical Hospital	Nalchik
Russian Federation	District Children's Clinic Hospital	Nizhnevartovsk
Russian Federation	Regional Children's Clinic Hospital	Nizhny Novgorod
Russian Federation	Municipal Children's Clinic Hospital ?4	Novokuznetsk
Russian Federation	Novosibirsk Central District Hospital	Novosibirsk
Russian Federation	Regional Clinical Oncology Dispensary	Orenburg
Russian Federation	Perm Regional Children's Clinic Hospital	Perm
Russian Federation	Regional Children's Hospital	Rostov-on-Don
Russian Federation	Rostov Research Institute of Oncology	Rostov-on-Don
Russian Federation	N. Dmitrieva Ryazan Regional Children's Hospital	Ryazan
Russian Federation	Children's Municipal Hospital ?1	Saint Petersburg
Russian Federation	Municipal Hospital ?31	Saint Petersburg
Russian Federation	R. Gorbacheva Research Institute of Pediatric Hematology and Transfusiology; Pavlov State Medical University of Saint-Petersburg	Saint Petersburg
Russian Federation	Children's Municipal Clinical Hospital ?1	Samara
Russian Federation	Profpathology and Hematology Clinic; Saratov State Medical University	Saratov
Russian Federation	Regional Children's Clinical Hospital	Stavropol
Russian Federation	Surgut Central District Clinical Hospital	Surgut
Russian Federation	Tomsk Regional Clinical Hospital	Tomsk
Russian Federation	Tula Regional Children's Hospital	Tula
Russian Federation	Republic Children's Clinical Hospital	Ulan-Ude
Russian Federation	Ulyanovsk Regional Children's Clinical Hospital	Ulyanovsk
Russian Federation	Municipal Children's City Hospital, Territorial Children's Hematological Center	Vladivostok
Russian Federation	Voronezh Regional Children Clinical Hospital ?1	Voronezh
Russian Federation	Republic Hospital ?1 - National Medicine Centre	Yakutsk
Russian Federation	Regional Children's Clinical Hospital	Yaroslavl
Russian Federation	Regional Children's Clinical Hospital ? 1	Yekaterinburg
Uzbekistan	Research Institute of Hematology and Blood Transfusion	Tashkent

Sponsors (1)

Lead Sponsor	Collaborator
Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Countries where clinical trial is conducted

Belarus,  Russian Federation,  Uzbekistan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free survival		3 years, 5 years and 10 years after study start
Primary	overall survival		3 years, 5 years and 10 years after study start
Primary	cumulative incidence of relapse		3 years, 5 years and 10 years after study start
Secondary	early death rate		3 years, 5 years and 10 years after study start
Secondary	remission death rate		3 years, 5 years and 10 years after study start

External Links

•   Study web-site