Childhood Acute Lymphoblastic Leukemia Treatment Protocol Moscow-Berlin 2015 (ALL-MB 2015)

NCT03390387 | Unknown DMC

• 1 other identifier: ALL-MB 2015
• Study Type: interventional
• Target: 4,000
• Locations: 5 countries
• Sites: 58

Brief Summary

QUESTIONS AND OBJECTIVES OF ALL-MB 2015 STUDY

1. 1.Will the new risk group stratification (especially of T-ALL) to improve overall and event-free survival?
2. 2.Will the new protocol is effective and feasible in patients older than 15 years, and especially in young adults?
3. 3.Whether the intermittent dexamethasone administration in induction will result in a decrease in toxicity and mortality without loss of efficacy?
4. 4.Whether the methylprednisolone administration as basic glucocorticoids during induction, consolidation and maintenance therapy will lead to decrease of severe infections and early mortality rate, improve survival and therapy compliance in adolescents and young adults with B-precursor ALL?
5. 5.Whether the administration of Bortezomib in patients with B-precursor ALL with initial WBC≥100,000/µl will improve treatment outcome?
6. 6.Whether the administration of Idarubicin instead Daunorubicin in low-risk T-ALL patients and two-phase induction in intermediate-risk T-ALL patients will reduce relapse rate and improve survival?

Conditions

Childhood Acute Lymphoblastic Leukemia

Keywords

Acute lymphoblastic leukemia, children, adolescents, treatment

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 (10)

Dexa intermittent

EXPERIMENTAL

Induction therapy with intermittent Dexamethasone administration (1-15 days - 6 mg/m2, 15-22 day - pause, 22-29 days - 6 mg/m2).

Drug: Dexamethasone intermittent

Dexa constant

ACTIVE COMPARATOR

Induction therapy with continuous Dexamethasone administration (6 mg/m2 1-29 days).

Drug: Dexamethasone continuous

Dexa

ACTIVE COMPARATOR

Therapy with Dexamethasone (6 mg/m2) as basic glucocorticoid preparation.

Drug: Dexamethasone

Medrol

EXPERIMENTAL

Therapy with Methylprednisolone (60 mg/m2) as basic glucocorticoid preparation.

Drug: Methylprednisolone

IDA

EXPERIMENTAL

Induction and consolidation therapy with Idarubicin

Drug: Idarubicin

DNR

ACTIVE COMPARATOR

Induction and consolidation therapy with Daunorubicin

Drug: Daunorubicin

Protocol Ib+

EXPERIMENTAL

Two-phase induction therapy (additional second phase of induction - protocol Ib)

Drug: Second phase of induction

Protocol Ib-

ACTIVE COMPARATOR

Standard induction therapy (without second phase)

Drug: Standard induction therapy

Bortezomib-

ACTIVE COMPARATOR

Consolidation therapy without Bortezomib

Drug: Standard consolidation therapy

Bortezomib+

EXPERIMENTAL

Consolidation therapy with Bortezomib 1.3 mg/m2 N12 (N4 in each reinduction)

Drug: Bortezomib

Interventions

Dexamethasone continuous DRUG

6 mg/m2, per os, in two divided doses per day q12 hours. 1-28 day (dose in the first few days is depending on the total tumor mass). From day 29 the dose of dexamethasone is reducing: days 29-31 - 3 mg/m2, days 32-34 - 1.5 mg/m2, days 35-36 - 0.75 mg/m2; then dexamethasone is discontinued completely.

Dexa constant

Dexamethasone intermittent DRUG

6 mg/m2, per os, in two divided doses per day q12 hours. Days: 1-14 (dose in the first few days is depending on the total tumor mass) and 22-28; days 15-21 - pause. From day 29 the dose of dexamethasone is reducing: days 29-30 - 3 mg/m2, days 31-32 - 1.5 mg/m2, then dexamethasone is discontinued completely.

Dexa intermittent

Dexamethasone DRUG

Induction: 6 mg/m2, per os, in two divided doses per day q12 hours. 1-28 day (dose in the first few days is depending on the total tumor mass). From day 29 the dose of dexamethasone is reducing: days 29-31 - 3 mg/m2, days 32-34 - 1.5 mg/m2, days 35-36 - 0.75 mg/m2; then dexamethasone is discontinued completely. Consolidation: 6 mg/m2 per os, in two divided doses per day q12 hours. Weeks 13-14 (days 85-98), weeks 21-22 (days 141-154), weeks 29-30 (days 197-210), weeks 37-38 (days 253-260), weeks 45-46 (days 309-316), weeks 53-54 (days 365-372). Maintenance therapy: 6 mg/m2, per os, in two divided doses per day q12 hours, for 10 days followed by quick discontinuation during 3 days. Weeks 61-62, 69-70, 77-78, 85-86, 93-94.

Dexa

Methylprednisolone DRUG

Induction: 60 mg/m2, per os, in two divided doses per day q12 hours. 1-28 day (dose in the first few days is depending on the total tumor mass). From day 29 the dose of dexamethasone is reducing: days 29-31 - 30 mg/m2, days 32-34 - 15 mg/m2, days 35-36 - 8 mg/m2; then methylprednisolone is discontinued completely. Consolidation: 60 mg/m2 per os, in two divided doses per day q12 hours. Weeks 13-14 (days 85-98), weeks 21-22 (days 141-154), weeks 29-30 (days 197-210), weeks 37-38 (days 253-260), weeks 45-46 (days 309-316), weeks 53-54 (days 365-372). Maintenance therapy: 60 mg/m2, per os, in two divided doses per day q12 hours, for 10 days followed by quick discontinuation during 3 days. Weeks 61-62, 69-70, 77-78, 85-86, 93-94.

Medrol

Daunorubicin DRUG

Induction: 45 mg/m2, intravenously, for 6 hours on days 8 and 22. Consolidation: 30 mg/m2, intravenously, for 6 hours on days 44, 65 (consolidation S1); 107, 121 (consolidation S2); and 163 (consolidation S3).

DNR

Idarubicin DRUG

Induction: 10 mg/m2, intravenously, for 6 hours on days 8 and 22. Consolidation: 8 mg/m2, intravenously, for 6 hours on days 44, 65 (consolidation S1); 107, 121 (consolidation S2); and 163 (consolidation S3).

IDA

Bortezomib DRUG

1.3 mg/м2, intravenously, bolus injection. Days 85, 89, 92, 96 (consolidation S1); 141, 145, 148, 152 (consolidation S2) and 197, 201, 204, 208 (consolidation S3).

Bortezomib+

Second phase of induction DRUG

Cyclophosphamide (1,000 mg/m2, intravenously, for 1 hour - days 43 and 71); Cytarabine (75 mg/m2/day, intravenously, bolus injection. Four blocks of 4 days each, days 46-48, 52-55, 59-62, and 66-69); 6-mercaptopurine (60 mg/m2/day, per os, days 43-71); Triple intrathecal therapy (days 52 and 66)

Protocol Ib+

Standard induction therapy DRUG

Dexamethasone (6 mg/m2, p/o; 1-29 days); Daunorubicin (45 mg/m2, i.v.; day 8 and 22); Vincristine (1.5 mg/m2, i.v.; days 8, 15, 22, 29 and 36); Triple intrathecal therapy (Methotrexate/Cytarabine/Prednisone; days 0/1, 8, 15, 22, 29 and 36)

Protocol Ib-

Standard consolidation therapy DRUG

Consolidation consists of 3 phases: S1, S2 and S3. Each phase is a 6-week therapy with 6-mercaptopurine (50 mg/m2 per day, daily, orally), methotrexate (30 мг/м2, i.m., weekly) and L-asparaginase (10 000 U/m2, i.m., weekly), followed by 2 weeks of re-induction with Vincristine (1.5 mg/m2, i.v., days 1 and 8 of reinduction) plus Dexamethasone (6 mg/m2, p/o, daily, for 10 days followed by quick discontinuation during 3 days). Daunorubicin (30 mg/м2, i.v., N2 during S1, N2 during S2 and N1 during S3). Triple intrathecal therapy (Methotrexate/Cytarabine/Prednisone) N12 (4 injections per each phase)

Bortezomib-

Eligibility Criteria

• Age: 1 Year - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age at diagnosis at 1 to 50 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 (see "Diagnostics"). Patients with B-cell (Burkitt) ALL are excluded.
• Informed consent of the patient parents (guardians) to be treated in one of the clinics included in this multicenter study.

You may not qualify if:

• ALL is a second malignancies;
• 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 data needed for the exact adherence to the cytostatic therapy according to a specific chemotherapy protocol (differential diagnosis of ALL-AML (acute myeloid leukemia) is not possible, stratification according to therapeutic group is not possible);
• The patient was treated before for a long time with cytotoxic drugs;
• There were treatment deviations 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 (58)

prof. R.O.Eolyan Hematology Center

Yerevan, Armenia

COMPLETED

Republican Research and Practical Center of Radiation Medicine and Human Ecology

Homyel, Belarus

RECRUITING

Republic Research and Practical Center of Pediatric Oncology, Hematology and Immunology

Minsk, Belarus

RECRUITING

Mogilev Regional Children's Hospital

Mogilev, Belarus

RECRUITING

National Oncology and Hematology Center, Ministry of Health of the Kyrgyz Republic

Bishkek, Kyrgyzstan

COMPLETED

Arkhangelsk Regional Clinical Children's Hospital

Arkhangelsk, Russia

RECRUITING

Regional Clinical Children's Hospital

Astrakhan, Russia

RECRUITING

Altay Regional Clinical Children's Hospital

Barnaul, Russia

RECRUITING

Amur Regional Clinical Children's Hospital

Blagoveshchensk, Russia

RECRUITING

Bryansk Regional Children's Hospital

Bryansk, Russia

RECRUITING

Chelyabinsk Regional Clinical Children's Hospital

Chelyabinsk, Russia

RECRUITING

Transbaikal Regional Oncology Dispensary

Chita, Russia

RECRUITING

Irkutsk Regional Children Clinical Hospital

Irkutsk, Russia

RECRUITING

Ivanovo Regional Clinical Hospital

Ivanovo, Russia

RECRUITING

Republic Clinical Children's Hospital

Izhevsk, Russia

RECRUITING

Regional Clinical Children's Hospital

Khabarovsk, Russia

RECRUITING

Kirov Research Institute of Hematology and Blood Transfusion

Kirov, Russia

RECRUITING

Regional Clinical Children's Hospital

Krasnodar, Russia

RECRUITING

Krasnoyarsk Territorial Clinical Children's Hospital

Krasnoyarsk, Russia

RECRUITING

Kurgan Regional Clinical Children's Hospital

Kurgan, Russia

RECRUITING

Regional Clinical Children's Hospital

Kursk, Russia

RECRUITING

Regional Children's Hospital

Lipetsk, Russia

RECRUITING

Republic Children's Clinical Hospital

Makhachkala, Russia

RECRUITING

Morozov Children's Municipal Clinical Hospital

Moscow, Russia

RECRUITING

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

Moscow, Russia

RECRUITING

Russian Children's Clinical Hospital

Moscow, Russia

RECRUITING

Murmansk Clinical Children's Hospital

Murmansk, Russia

RECRUITING

Republic Clinical Children's Hospital

Nal'chik, Russia

RECRUITING

Nizhnevartovsk Regional Clinical Children's Hospital

Nizhnevartovsk, Russia

RECRUITING

Regional Clinical Children's Hospital

Nizhny Novgorod, Russia

RECRUITING

Novokuznetsk Municipal Clinical Children's Hospital N4

Novokuznetsk, Russia

RECRUITING

Novosibirsk Central District Clinical Hospital

Novosibirsk, Russia

RECRUITING

Orenburg Regional Clinical Oncology Dispensary

Orenburg, Russia

RECRUITING

Regional Clinical Children's Hospital

Oryol, Russia

RECRUITING

Perm Territorial Clinical Children's Hospital

Perm, Russia

RECRUITING

Regional Clinical Children's Hospital

Rostov-on-Don, Russia

RECRUITING

Rostov Research Institute of Oncology

Rostov-on-Don, Russia

RECRUITING

N. Dmitrieva Ryazan Regional Clinical Children's Hospital

Ryazan, Russia

RECRUITING

Almazov National Medical Research Center

Saint Petersburg, Russia

RECRUITING

Children's Municipal Hospital N1

Saint Petersburg, Russia

RECRUITING

Municipal Clinical Hospital N31

Saint Petersburg, Russia

RECRUITING

N.N.Petrov National Medical Research Oncology Center

Saint Petersburg, Russia

RECRUITING

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

Saint Petersburg, Russia

RECRUITING

Municipal Clinical Children's Hospital N1

Samara, Russia

RECRUITING

Regional Children's Clinical Hospital

Stavropol, Russia

RECRUITING

Surgut Regional Clinical Hospital

Surgut, Russia

COMPLETED

Republic Clinical Children's Hospital

Syktyvkar, Russia

RECRUITING

Tomsk Regional Clinical Hospital

Tomsk, Russia

RECRUITING

Tula Regional Clinical Children's Hospital

Tula, Russia

RECRUITING

Republic Clinical Children's Hospital

Ulan-Ude, Russia

RECRUITING

Ulyanovsk Regional Children's Clinical Hospital

Ulyanovsk, Russia

RECRUITING

Regional Children's Clinical Hospital N1, Territorial Children's Hematological Center

Vladivostok, Russia

RECRUITING

Vologda Regional Clinical Children's Hospital

Vologda, Russia

RECRUITING

Voronezh Regional Clinical Children's Hospital N1

Voronezh, Russia

RECRUITING

Republic Hospital N1 - National Medicine Centre

Yakutsk, Russia

RECRUITING

Regional Clinical Children's Hospital

Yaroslavl, Russia

RECRUITING

Regional Clinical Children's Hospital N1; Children Oncology and hematology Center

Yekaterinburg, Russia

RECRUITING

Research Institute of Hematology and Blood Transfusion

Tashkent, Uzbekistan

RECRUITING

Related Links

• Study web-site

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Dexamethasone; Methylprednisolone; Daunorubicin; Idarubicin; Bortezomib

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)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Prednisolone; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Aminoglycosides; Glycosides; Carbohydrates; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Alexander I. Karachunskiy, Professor, MD

  Research Institute of Pediatric Hematology, Oncology and Immunology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alexander I. Karachunskiy, Professor, MD

CONTACT

+7-926-218-84-09; info@mbstudy.net

Julia V. Roumiantseva, MD. PhD

CONTACT

+7-903-730-39-78; j.roumiantseva@mbstudy.net

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy director - Director of Institute of Oncology, Radiology and Nuclear Medicine of Federal Research Institute of Pediatric hematology, Oncology and Immunology

Study Record Dates

• First Submitted: December 27, 2017
• First Posted: January 4, 2018
• Study Start: November 1, 2015
• Primary Completion: November 1, 2020
• Study Completion: November 1, 2025
• Last Updated: February 5, 2020

Record last verified: 2020-02

Locations

AR (1); BE (3); KY (1); RU (52); UZ (1)