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

Childhood Acute Lymphoblastic Leukemia Clinical Trial

— ALL-MB 2015  

Official title:

Moscow-Berlin 2015 Multicenter Randomized Study for Treatment of Acute Lymphoblastic Leukemia in Children, Adolescents and Young Adults

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03390387
• Other study ID #: ALL-MB 2015
• Status: Recruiting
• Phase: N/A
• Start date: November 2015
• Est. completion date: November 2025

Study information

• Verified date: February 2020
• Source: Federal Research Institute of Pediatric Hematology, Oncology and Immunology
• Contact: Alexander I. Karachunskiy, Professor, MD
• Phone: +7-926-218-84-09
• Email: info[@]mbstudy.net
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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?

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 4000
• Est. completion date: November 2025
• Est. primary completion date: November 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 50 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• 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.
• 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.
• 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.
• 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.
• 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).
• 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).
• Bortezomib
1.3 mg/?2, intravenously, bolus injection. Days 85, 89, 92, 96 (consolidation S1); 141, 145, 148, 152 (consolidation S2) and 197, 201, 204, 208 (consolidation S3).
• 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)
• 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)
• 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 ??/?2, 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/?2, i.v., N2 during S1, N2 during S2 and N1 during S3). Triple intrathecal therapy (Methotrexate/Cytarabine/Prednisone) N12 (4 injections per each phase)

Locations

Country	Name	City	State
Armenia	prof. R.O.Eolyan Hematology Center	Ereván
Belarus	Republican Research and Practical Center of Radiation Medicine and Human Ecology	Gomel
Belarus	Republic Research and Practical Center of Pediatric Oncology, Hematology and Immunology	Minsk
Belarus	Mogilev Regional Children's Hospital	Mogilev
Kyrgyzstan	National Oncology and Hematology Center, Ministry of Health of the Kyrgyz Republic	Bishkek
Russian Federation	Arkhangelsk Regional Clinical Children's Hospital	Arkhangelsk
Russian Federation	Regional Clinical Children's Hospital	Astrakhan
Russian Federation	Altay Regional Clinical Children's Hospital	Barnaul
Russian Federation	Amur Regional Clinical Children's Hospital	Blagoveshchensk
Russian Federation	Bryansk Regional Children's Hospital	Bryansk
Russian Federation	Chelyabinsk Regional Clinical Children's Hospital	Chelyabinsk
Russian Federation	Transbaikal Regional Oncology Dispensary	Chita
Russian Federation	Irkutsk Regional Children Clinical Hospital	Irkutsk
Russian Federation	Ivanovo Regional Clinical Hospital	Ivanovo
Russian Federation	Republic Clinical Children's Hospital	Izhevsk
Russian Federation	Regional Clinical Children's Hospital	Khabarovsk
Russian Federation	Kirov Research Institute of Hematology and Blood Transfusion	Kirov
Russian Federation	Regional Clinical Children's Hospital	Krasnodar
Russian Federation	Krasnoyarsk Territorial Clinical Children's Hospital	Krasnoyarsk
Russian Federation	Kurgan Regional Clinical Children's Hospital	Kurgan
Russian Federation	Regional Clinical Children's Hospital	Kursk
Russian Federation	Regional Children's Hospital	Lipetsk
Russian Federation	Republic Children's Clinical Hospital	Makhachkala
Russian Federation	Morozov Children's Municipal Clinical Hospital	Moscow
Russian Federation	Research Institute of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogachev	Moscow
Russian Federation	Russian Children's Clinical Hospital	Moscow
Russian Federation	Murmansk Clinical Children's Hospital	Murmansk
Russian Federation	Republic Clinical Children's Hospital	Nal'chik
Russian Federation	Nizhnevartovsk Regional Clinical Children's Hospital	Nizhnevartovsk
Russian Federation	Regional Clinical Children's Hospital	Nizhny Novgorod
Russian Federation	Novokuznetsk Municipal Clinical Children's Hospital N4	Novokuznetsk
Russian Federation	Novosibirsk Central District Clinical Hospital	Novosibirsk
Russian Federation	Regional Clinical Children's Hospital	Orël
Russian Federation	Orenburg Regional Clinical Oncology Dispensary	Orenburg
Russian Federation	Perm Territorial Clinical Children's Hospital	Perm
Russian Federation	Regional Clinical Children's Hospital	Rostov-on-Don
Russian Federation	Rostov Research Institute of Oncology	Rostov-on-Don
Russian Federation	N. Dmitrieva Ryazan Regional Clinical Children's Hospital	Ryazan
Russian Federation	Almazov National Medical Research Center	Saint Petersburg
Russian Federation	Children's Municipal Hospital N1	Saint Petersburg
Russian Federation	Municipal Clinical Hospital N31	Saint Petersburg
Russian Federation	N.N.Petrov National Medical Research Oncology Center	Saint Petersburg
Russian Federation	R. Gorbacheva Research Institute of Pediatric Hematology and Transfusiology; Pavlov First Saint-Petersburg State Medical University	Saint Petersburg
Russian Federation	Municipal Clinical Children's Hospital N1	Samara
Russian Federation	Regional Children's Clinical Hospital	Stavropol
Russian Federation	Surgut Regional Clinical Hospital	Surgut
Russian Federation	Republic Clinical Children's Hospital	Syktyvkar
Russian Federation	Tomsk Regional Clinical Hospital	Tomsk
Russian Federation	Tula Regional Clinical Children's Hospital	Tula
Russian Federation	Republic Clinical Children's Hospital	Ulan-Ude
Russian Federation	Ulyanovsk Regional Children's Clinical Hospital	Ulyanovsk
Russian Federation	Regional Children's Clinical Hospital N1, Territorial Children's Hematological Center	Vladivostok
Russian Federation	Vologda Regional Clinical Children's Hospital	Vologda
Russian Federation	Voronezh Regional Clinical Children's Hospital N1	Voronezh
Russian Federation	Republic Hospital N1 - National Medicine Centre	Yakutsk
Russian Federation	Regional Clinical Children's Hospital	Yaroslavl
Russian Federation	Regional Clinical Children's Hospital N1; Children Oncology and hematology Center	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

Armenia,  Belarus,  Kyrgyzstan,  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