Childhood Acute Lymphoblastic Leukemia Treatment Protocol Moscow-Berlin 2008

NCT01953770 | Unknown DMC

• 1 other identifier: ALL-MB 2008
• Study Type: interventional
• Target: 3,000
• Locations: 3 countries
• Sites: 46

Brief Summary

QUESTIONS AND OBJECTIVES OF ALL-MB-2008 STUDY

1. 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. 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. 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. 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. 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. 6.Will the new risk group stratification to improve overall and event-free survival?

Conditions

Childhood Acute Lymphoblastic Leukemia

Keywords

Acute lymphoblastic leukemia, children, adolescents, L-asparaginase, methotrexate

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (2)

• 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

Study Arms (9)

Cranial irradiation

ACTIVE COMPARATOR

Consolidation therapy with cranial irradiation in intermediate risk group patients

Radiation: Cranial irradiation

Additional TIT

EXPERIMENTAL

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

Drug: Triple intrathecal therapy

MTX 2,000 mg/m2

EXPERIMENTAL

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

Drug: High-dose Methotrexate

MTX 30 mg/m2

ACTIVE COMPARATOR

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

Drug: Low-dose Methotrexate

PEG-asp 1,000 U/m2

EXPERIMENTAL

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

Drug: PEG-L-asparaginase cons

L-asp 5,000 U/m2

ACTIVE COMPARATOR

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

Drug: E.coli L-asparaginase

PEG-DNR+

ACTIVE COMPARATOR

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

Drug: Daunorubicin

PEG+DNR+

EXPERIMENTAL

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

Drug: PEG-L-asparaginase ind; Drug: Daunorubicin

PEG+DNR-

EXPERIMENTAL

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

Drug: PEG-L-asparaginase ind

Interventions

PEG-L-asparaginase ind DRUG

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

PEG+DNR+; PEG+DNR-

PEG-L-asparaginase cons 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).

PEG-asp 1,000 U/m2

E.coli L-asparaginase 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).

Also known as: Asparaginase Medac

L-asp 5,000 U/m2

High-dose Methotrexate 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 2,000 mg/m2

Low-dose Methotrexate 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).

MTX 30 mg/m2

Triple intrathecal therapy 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).

Also known as: Methotrexate/Cytarabine/Prednisone i.th.

Additional TIT

Cranial irradiation RADIATION

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

Cranial irradiation

Daunorubicin DRUG

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

PEG+DNR+; PEG-DNR+

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Federal Research Institute of Pediatric Hematology, Oncology and Immunology: lead

Study Sites (46)

Republican Research and Practical Center of Radiation Medicine

Homyel, Belarus

Location

Republic Research and Practical Center of Pediatric Oncology and Hematology

Minsk, Belarus

Location

Mogilev Regional Children's Hospital

Mogilev, Belarus

Location

Arkhangelsk Regional Children's Hospital

Arkhangelsk, Russia

Location

Regional Children's Hospital

Astrakhan, Russia

Location

Moscow Regional Cancer Dispensary

Balashikha, Russia

Location

Amur Regional Children's Hospital

Blagoveshchensk, Russia

Location

Chelyabinsk Regional Children's Clinical Hospital

Chelyabinsk, Russia

Location

Irkutsk Regional Children Clinical Hospital

Irkutsk, Russia

Location

Regional Clinical Hospital

Ivanovo, Russia

Location

Regional Children's Clinical Hospital

Khabarovsk, Russia

Location

Kirov Research Institute of Hematology and Blood Transfusion

Kirov, Russia

Location

Regional Children's Hospital

Krasnodar, Russia

Location

Krasnoyarsk Territorial Clinical Children Hospital

Krasnoyarsk, Russia

Location

Regional Children's Hospital

Kursk, Russia

Location

Republic Children's Clinical Hospital

Makhachkala, Russia

Location

Morozov Children's Clinical Hospital

Moscow, Russia

Location

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

Moscow, Russia

Location

Russian Children's Clinic Hospital

Moscow, Russia

Location

Republic Children's Clinical Hospital

Nal'chik, Russia

Location

District Children's Clinic Hospital

Nizhnevartovsk, Russia

Location

Regional Children's Clinic Hospital

Nizhny Novgorod, Russia

Location

Municipal Children's Clinic Hospital №4

Novokuznetsk, Russia

Location

Novosibirsk Central District Hospital

Novosibirsk, Russia

Location

Regional Clinical Oncology Dispensary

Orenburg, Russia

Location

Perm Regional Children's Clinic Hospital

Perm, Russia

Location

Regional Children's Hospital

Rostov-on-Don, Russia

Location

Rostov Research Institute of Oncology

Rostov-on-Don, Russia

Location

N. Dmitrieva Ryazan Regional Children's Hospital

Ryazan, Russia

Location

Children's Municipal Hospital №1

Saint Petersburg, Russia

Location

Municipal Hospital №31

Saint Petersburg, Russia

Location

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

Saint Petersburg, Russia

Location

Children's Municipal Clinical Hospital №1

Samara, Russia

Location

Profpathology and Hematology Clinic; Saratov State Medical University

Saratov, Russia

Location

Regional Children's Clinical Hospital

Stavropol, Russia

Location

Surgut Central District Clinical Hospital

Surgut, Russia

Location

Tomsk Regional Clinical Hospital

Tomsk, Russia

Location

Tula Regional Children's Hospital

Tula, Russia

Location

Republic Children's Clinical Hospital

Ulan-Ude, Russia

Location

Ulyanovsk Regional Children's Clinical Hospital

Ulyanovsk, Russia

Location

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

Vladivostok, Russia

Location

Voronezh Regional Children Clinical Hospital №1

Voronezh, Russia

Location

Republic Hospital №1 - National Medicine Centre

Yakutsk, Russia

Location

Regional Children's Clinical Hospital

Yaroslavl, Russia

Location

Regional Children's Clinical Hospital № 1

Yekaterinburg, Russia

Location

Research Institute of Hematology and Blood Transfusion

Tashkent, Uzbekistan

Location

Related Links

• Study web-site

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Asparaginase; Methotrexate; Cranial Irradiation; Daunorubicin

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Amidohydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Radiotherapy; Therapeutics; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Alexander I. Karachunskiy, Professor

  Research Institute of Pediatric Hematology, Oncology and Immunology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy director of Research Institute of Pediatric Hematology, Oncology and Immunology

Study Record Dates

• First Submitted: September 26, 2013
• First Posted: October 1, 2013
• Study Start: February 1, 2008
• Primary Completion: January 1, 2015
• Study Completion: July 1, 2020
• Last Updated: February 5, 2020

Record last verified: 2020-02

Locations

UZ (1); BE (3); RU (42)