Treatment Protocol for Children and Adolescents With Acute Lymphoblastic Leukemia - AIEOP-BFM ALL 2017

Summary

The understanding of acute lymphoblastic leukemia (ALL) in childhood and adolescence has largely changed due to extensive genetic research in recent years: ALL is now considered to be a very heterogeneous disease group. The leukemia cells present themselves with quite differently activated regulatory mechanisms of the malignant phenotype. The introduction of more accurate methods of assessing therapy response ("minimal residual disease \[MRD\] tests") has provided new insights into very different mechanisms of action, including factors influenced by host factors; this has had practical clinical consequences for the use of more individualized therapy. Multimodal therapies have enabled a cure level of over 80% for ALL in this age group. However, the own and international study data show that the therapy toxicity of the contemporary chemotherapy concepts has become unacceptably high, in particular with respect to those intensified therapies used for the treatment of patients at high risk of ALL relapse.

The AIEOP-BFM ALL 2017 study therefore aims for an innovative integrated approach that will not only adapt the risk stratification to new prognostic markers using more comprehensive diagnostics, but above all, qualitatively reorient the therapy. The most important consequence will be that this study is testing immunotherapy with the bispecific antibody blinatumomab as an alternative to particularly intensive and toxic chemotherapy elements in precursor B-cell ALL (pB-ALL) patients with detectable chemotherapy resistance and at high risk of relapse. With the aim to complement the effects of the conventional chemotherapy, Blinatumomab is in addition tested in the large group of pB-ALL patients at intermediate relapse risk with seemingly unremarkable leukemia, but who account for a large proportion of all relapses. Targeted therapy is also used in the form of the proteasome inhibitor bortezomib for patients with pB-ALL and slow response to the drugs of the induction chemotherapy with the aim to overcome intrinsic chemotherapy resistance of the ALL cells. In patients with T-lineage ALL, who have particularly poor chances for cure after relapse, the established consolidation chemotherapy has proved to be particularly effective. This chemotherapy phase is therefore tested in a longer and more intensive form in such T-ALL patients with intermediate or slow early treatment response with the aim to reduce the relapses rate in this subgroup.

Conditions

• Acute Lymphoblastic Leukemia, Pediatric

Interventions

DRUG

Blinatumomab

Experimental therapy in randomizations R-HR and R-MR

DRUG

Bortezomib

Experimental therapy in randomization R-eHR

DRUG

Cyclophosphamide

Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T

DRUG

Cytarabine

Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T and in the intensification block Myocet-FLA for patients with very high relapse risk

DRUG

Daunorubicin

Part of standard chemotherapy

DRUG

Myocet

Part of intensification block Myocet-FLA for patients with very high relapse risk

DRUG

Dexamethasone

Part of standard chemotherapy

DRUG

Doxorubicin

Part of standard chemotherapy

DRUG

Etoposide

Part of standard chemotherapy

DRUG

Fludarabine Phosphate

Part of intensification block Myocet-FLA for patients with very high relapse risk

DRUG

Ifosfamide

Part of standard chemotherapy

DRUG

6-Mercaptopurine

Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T

DRUG

Methotrexate

Part of standard chemotherapy

DRUG

Pegaspargase

Part of standard chemotherapy

DRUG

Prednisolone

Part of standard chemotherapy

DRUG

Tioguanin

Part of standard chemotherapy

DRUG

Vincristine

Part of standard chemotherapy

DRUG

Vindesine

Part of standard chemotherapy

DRUG

Erwinase

Part of standard chemotherapy as substitute for PEG-L-Asparaginase in case of allergic reaction

Sponsors & Collaborators

• Deutsche Krebshilfe e.V., Bonn (Germany)

  collaborator OTHER

• Martin Schrappe

  lead OTHER

Principal Investigators

• Martin Schrappe, MD · Department of Pediatrics, University Hospital of Schleswig-Holstein, Campus Kiel

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

FACTORIAL

Eligibility

Max Age

17 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-07-15

Primary Completion

2028-07-14

Completion

2028-07-14

Countries

• Australia
• Austria
• Czechia
• Germany
• Israel
• Italy
• Slovakia
• Switzerland

Study Locations