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

Condition(s) studied

Investigational drug(s) / intervention(s)

Blinatumomab: Experimental therapy in randomizations R-HR and R-MR

Bortezomib: Experimental therapy in randomization R-eHR

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

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

Daunorubicin: Part of standard chemotherapy

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

Dexamethasone: Part of standard chemotherapy

Doxorubicin: Part of standard chemotherapy

Etoposide: Part of standard chemotherapy

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

Ifosfamide: Part of standard chemotherapy

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

Methotrexate: Part of standard chemotherapy

Pegaspargase: Part of standard chemotherapy

Prednisolone: Part of standard chemotherapy

Tioguanin: Part of standard chemotherapy

Vincristine: Part of standard chemotherapy

Vindesine: Part of standard chemotherapy

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

Study 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.

Eligibility

Primary outcome measure(s)

• Event-free survival — Assessed up to 120 months from start of study
  Randomization R-eHR, R-HR and R-T: Time from randomization until the first event defined as follow: cytomorphological or molecular non-response (resistance to protocol treatment, considered as event at day zero), relapse, second malignancy or death from any cause. This will be called EFS time.
• Disease-free survival — Assessed up to 120 months from start of study
  Randomization R-MR: Time from randomization until the first event defined as follow: Relapse, second malignancy or death from any cause. This will be called DFS time.

Trial sites (115)

+ 75 more sites — see the full list on the official registry below.