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

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ClinicalTrials.gov Identifier: NCT03390387
Recruitment Status : Recruiting
First Posted : January 4, 2018
Last Update Posted : January 10, 2018
Sponsor:
Information provided by (Responsible Party):
Karachunskiy Alexander, Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Brief 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?

Condition or disease Intervention/treatment Phase
Childhood Acute Lymphoblastic Leukemia Drug: Dexamethasone continuous Drug: Dexamethasone intermittent Drug: Dexamethasone Drug: Methylprednisolone Drug: Daunorubicin Drug: Idarubicin Drug: Bortezomib Drug: Second phase of induction Drug: Standard induction therapy Drug: Standard consolidation therapy Not Applicable

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 4000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Moscow-Berlin 2015 Multicenter Randomized Study for Treatment of Acute Lymphoblastic Leukemia in Children, Adolescents and Young Adults
Actual Study Start Date : November 2015
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : November 2025


Arm Intervention/treatment
Experimental: Dexa intermittent
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
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.

Active Comparator: Dexa constant
Induction therapy with continuous Dexamethasone administration (6 mg/m2 1-29 days).
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.

Active Comparator: Dexa
Therapy with Dexamethasone (6 mg/m2) as basic glucocorticoid preparation.
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.


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


Experimental: IDA
Induction and consolidation therapy with Idarubicin
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).

Active Comparator: DNR
Induction and consolidation therapy with Daunorubicin
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).

Experimental: Protocol Ib+
Two-phase induction therapy (additional second phase of induction - protocol Ib)
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)

Active Comparator: Protocol Ib-
Standard induction therapy (without second phase)
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)

Active Comparator: Bortezomib-
Consolidation therapy without Bortezomib
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)

Experimental: Bortezomib+
Consolidation therapy with Bortezomib 1.3 mg/m2 N12 (N4 in each reinduction)
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).




Primary Outcome Measures :
  1. Event-free survival [ Time Frame: 3 years, 5 years and 10 years after study start ]
  2. Overall survival [ Time Frame: 3 years, 5 years and 10 years after study start ]
  3. Cumulative incidence of relapse [ Time Frame: 3 years, 5 years and 10 years after study start ]

Secondary Outcome Measures :
  1. Early death rate [ Time Frame: 3 years, 5 years and 10 years after study start ]
  2. Remission death rate [ Time Frame: 3 years, 5 years and 10 years after study start ]


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Ages Eligible for Study:   1 Year to 50 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03390387


Contacts
Contact: Alexander I. Karachunskiy, Professor, MD +7-926-218-84-09 info@mbstudy.net
Contact: Julia V. Roumiantseva, MD. PhD +7-903-730-39-78 j.roumiantseva@mbstudy.net

  Show 58 Study Locations
Sponsors and Collaborators
Federal Research Institute of Pediatric Hematology, Oncology and Immunology
Investigators
Principal Investigator: Alexander I. Karachunskiy, Professor, MD Research Institute of Pediatric Hematology, Oncology and Immunology

Additional Information:
Responsible Party: Karachunskiy Alexander, Deputy director - Director of Institute of Oncology, Radiology and Nuclear Medicine of Federal Research Institute of Pediatric hematology, Oncology and Immunology, Federal Research Institute of Pediatric Hematology, Oncology and Immunology
ClinicalTrials.gov Identifier: NCT03390387     History of Changes
Other Study ID Numbers: ALL-MB 2015
First Posted: January 4, 2018    Key Record Dates
Last Update Posted: January 10, 2018
Last Verified: January 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Karachunskiy Alexander, Federal Research Institute of Pediatric Hematology, Oncology and Immunology:
Acute lymphoblastic leukemia, children, adolescents, treatment

Additional relevant MeSH terms:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Prednisolone acetate
Methylprednisolone acetate
Dexamethasone
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Glucocorticoids
Bortezomib
Daunorubicin
Idarubicin
6-Mercaptopurine
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents