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

NCT ID: NCT03390387

Last Updated: 2020-02-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

4000 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-11-30

Study Completion Date

2025-11-30

Brief Summary

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QUESTIONS AND OBJECTIVES OF ALL-MB 2015 STUDY

1. Will the new risk group stratification (especially of T-ALL) to improve overall and event-free survival?
2. Will the new protocol is effective and feasible in patients older than 15 years, and especially in young adults?
3. Whether the intermittent dexamethasone administration in induction will result in a decrease in toxicity and mortality without loss of efficacy?
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. Whether the administration of Bortezomib in patients with B-precursor ALL with initial WBC≥100,000/µl will improve treatment outcome?
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?

Detailed Description

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Conditions

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Childhood Acute Lymphoblastic Leukemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dexa intermittent

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

Group Type EXPERIMENTAL

Dexamethasone intermittent

Intervention Type 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 constant

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

Group Type ACTIVE_COMPARATOR

Dexamethasone continuous

Intervention Type 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

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

Group Type ACTIVE_COMPARATOR

Dexamethasone

Intervention Type 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.

Medrol

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

Group Type EXPERIMENTAL

Methylprednisolone

Intervention Type 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.

IDA

Induction and consolidation therapy with Idarubicin

Group Type EXPERIMENTAL

Idarubicin

Intervention Type 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).

DNR

Induction and consolidation therapy with Daunorubicin

Group Type ACTIVE_COMPARATOR

Daunorubicin

Intervention Type 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).

Protocol Ib+

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

Group Type EXPERIMENTAL

Second phase of induction

Intervention Type 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 (without second phase)

Group Type ACTIVE_COMPARATOR

Standard induction therapy

Intervention Type 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)

Bortezomib-

Consolidation therapy without Bortezomib

Group Type ACTIVE_COMPARATOR

Standard consolidation therapy

Intervention Type 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+

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

Group Type EXPERIMENTAL

Bortezomib

Intervention Type 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).

Interventions

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Dexamethasone continuous

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.

Intervention Type DRUG

Dexamethasone intermittent

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.

Intervention Type DRUG

Dexamethasone

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.

Intervention Type DRUG

Methylprednisolone

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.

Intervention Type DRUG

Daunorubicin

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).

Intervention Type DRUG

Idarubicin

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).

Intervention Type DRUG

Bortezomib

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).

Intervention Type DRUG

Second phase of induction

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)

Intervention Type DRUG

Standard induction therapy

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)

Intervention Type DRUG

Standard consolidation therapy

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)

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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
Minimum Eligible Age

1 Year

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Federal Research Institute of Pediatric Hematology, Oncology and Immunology

OTHER

Sponsor Role lead

Responsible Party

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Karachunskiy Alexander

Deputy director - Director of Institute of Oncology, Radiology and Nuclear Medicine of Federal Research Institute of Pediatric hematology, Oncology and Immunology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Alexander I. Karachunskiy, Professor, MD

Role: PRINCIPAL_INVESTIGATOR

Research Institute of Pediatric Hematology, Oncology and Immunology

Locations

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prof. R.O.Eolyan Hematology Center

Yerevan, , Armenia

Site Status COMPLETED

Republican Research and Practical Center of Radiation Medicine and Human Ecology

Homyel, , Belarus

Site Status RECRUITING

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

Minsk, , Belarus

Site Status RECRUITING

Mogilev Regional Children's Hospital

Mogilev, , Belarus

Site Status RECRUITING

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

Bishkek, , Kyrgyzstan

Site Status COMPLETED

Arkhangelsk Regional Clinical Children's Hospital

Arkhangelsk, , Russia

Site Status RECRUITING

Regional Clinical Children's Hospital

Astrakhan, , Russia

Site Status RECRUITING

Altay Regional Clinical Children's Hospital

Barnaul, , Russia

Site Status RECRUITING

Amur Regional Clinical Children's Hospital

Blagoveshchensk, , Russia

Site Status RECRUITING

Bryansk Regional Children's Hospital

Bryansk, , Russia

Site Status RECRUITING

Chelyabinsk Regional Clinical Children's Hospital

Chelyabinsk, , Russia

Site Status RECRUITING

Transbaikal Regional Oncology Dispensary

Chita, , Russia

Site Status RECRUITING

Irkutsk Regional Children Clinical Hospital

Irkutsk, , Russia

Site Status RECRUITING

Ivanovo Regional Clinical Hospital

Ivanovo, , Russia

Site Status RECRUITING

Republic Clinical Children's Hospital

Izhevsk, , Russia

Site Status RECRUITING

Regional Clinical Children's Hospital

Khabarovsk, , Russia

Site Status RECRUITING

Kirov Research Institute of Hematology and Blood Transfusion

Kirov, , Russia

Site Status RECRUITING

Regional Clinical Children's Hospital

Krasnodar, , Russia

Site Status RECRUITING

Krasnoyarsk Territorial Clinical Children's Hospital

Krasnoyarsk, , Russia

Site Status RECRUITING

Kurgan Regional Clinical Children's Hospital

Kurgan, , Russia

Site Status RECRUITING

Regional Clinical Children's Hospital

Kursk, , Russia

Site Status RECRUITING

Regional Children's Hospital

Lipetsk, , Russia

Site Status RECRUITING

Republic Children's Clinical Hospital

Makhachkala, , Russia

Site Status RECRUITING

Morozov Children's Municipal Clinical Hospital

Moscow, , Russia

Site Status RECRUITING

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

Moscow, , Russia

Site Status RECRUITING

Russian Children's Clinical Hospital

Moscow, , Russia

Site Status RECRUITING

Murmansk Clinical Children's Hospital

Murmansk, , Russia

Site Status RECRUITING

Republic Clinical Children's Hospital

Nal'chik, , Russia

Site Status RECRUITING

Nizhnevartovsk Regional Clinical Children's Hospital

Nizhnevartovsk, , Russia

Site Status RECRUITING

Regional Clinical Children's Hospital

Nizhny Novgorod, , Russia

Site Status RECRUITING

Novokuznetsk Municipal Clinical Children's Hospital N4

Novokuznetsk, , Russia

Site Status RECRUITING

Novosibirsk Central District Clinical Hospital

Novosibirsk, , Russia

Site Status RECRUITING

Orenburg Regional Clinical Oncology Dispensary

Orenburg, , Russia

Site Status RECRUITING

Regional Clinical Children's Hospital

Oryol, , Russia

Site Status RECRUITING

Perm Territorial Clinical Children's Hospital

Perm, , Russia

Site Status RECRUITING

Regional Clinical Children's Hospital

Rostov-on-Don, , Russia

Site Status RECRUITING

Rostov Research Institute of Oncology

Rostov-on-Don, , Russia

Site Status RECRUITING

N. Dmitrieva Ryazan Regional Clinical Children's Hospital

Ryazan, , Russia

Site Status RECRUITING

Almazov National Medical Research Center

Saint Petersburg, , Russia

Site Status RECRUITING

Children's Municipal Hospital N1

Saint Petersburg, , Russia

Site Status RECRUITING

Municipal Clinical Hospital N31

Saint Petersburg, , Russia

Site Status RECRUITING

N.N.Petrov National Medical Research Oncology Center

Saint Petersburg, , Russia

Site Status RECRUITING

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

Saint Petersburg, , Russia

Site Status RECRUITING

Municipal Clinical Children's Hospital N1

Samara, , Russia

Site Status RECRUITING

Regional Children's Clinical Hospital

Stavropol, , Russia

Site Status RECRUITING

Surgut Regional Clinical Hospital

Surgut, , Russia

Site Status COMPLETED

Republic Clinical Children's Hospital

Syktyvkar, , Russia

Site Status RECRUITING

Tomsk Regional Clinical Hospital

Tomsk, , Russia

Site Status RECRUITING

Tula Regional Clinical Children's Hospital

Tula, , Russia

Site Status RECRUITING

Republic Clinical Children's Hospital

Ulan-Ude, , Russia

Site Status RECRUITING

Ulyanovsk Regional Children's Clinical Hospital

Ulyanovsk, , Russia

Site Status RECRUITING

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

Vladivostok, , Russia

Site Status RECRUITING

Vologda Regional Clinical Children's Hospital

Vologda, , Russia

Site Status RECRUITING

Voronezh Regional Clinical Children's Hospital N1

Voronezh, , Russia

Site Status RECRUITING

Republic Hospital N1 - National Medicine Centre

Yakutsk, , Russia

Site Status RECRUITING

Regional Clinical Children's Hospital

Yaroslavl, , Russia

Site Status RECRUITING

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

Yekaterinburg, , Russia

Site Status RECRUITING

Research Institute of Hematology and Blood Transfusion

Tashkent, , Uzbekistan

Site Status RECRUITING

Countries

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Armenia Belarus Kyrgyzstan Russia Uzbekistan

Central Contacts

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Alexander I. Karachunskiy, Professor, MD

Role: CONTACT

+7-926-218-84-09

Julia V. Roumiantseva, MD. PhD

Role: CONTACT

+7-903-730-39-78

Related Links

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Other Identifiers

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ALL-MB 2015

Identifier Type: -

Identifier Source: org_study_id

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