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

Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Status: Enrolling

Conditions: Childhood Acute Lymphoblastic Leukemia

Treatments: Drug: Second phase of induction; Drug: Idarubicin; Drug: Standard consolidation therapy; Drug: Daunorubicin; Drug: Methylprednisolone; Drug: Bortezomib; Drug: Dexamethasone intermittent; Drug: Standard induction therapy; Drug: Dexamethasone; Drug: Dexamethasone continuous

Study type: Interventional

Funder types: Other

Identifiers

NCT03390387

ALL-MB 2015

Details and patient eligibility

About

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?

Enrollment: 4,000 estimated patients

Sex: All

Ages: 1 to 50 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

4,000 participants in 10 patient groups

Dexa intermittent

Experimental group

Description:

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

Treatment:

Drug: Dexamethasone intermittent

Dexa constant

Active Comparator group

Description:

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

Treatment:

Drug: Dexamethasone continuous

Dexa

Active Comparator group

Description:

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

Treatment:

Drug: Dexamethasone

Medrol

Experimental group

Description:

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

Treatment:

Drug: Methylprednisolone

IDA

Experimental group

Description:

Induction and consolidation therapy with Idarubicin

Treatment:

Drug: Idarubicin

DNR

Active Comparator group

Description:

Induction and consolidation therapy with Daunorubicin

Treatment:

Drug: Daunorubicin

Protocol Ib+

Experimental group

Description:

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

Treatment:

Drug: Second phase of induction

Protocol Ib-

Active Comparator group

Description:

Standard induction therapy (without second phase)

Treatment:

Drug: Standard induction therapy

Bortezomib-

Active Comparator group

Description:

Consolidation therapy without Bortezomib

Treatment:

Drug: Standard consolidation therapy

Bortezomib+

Experimental group

Description:

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

Treatment:

Drug: Bortezomib