Treatment Protocol for Children and Adolescents With Acute Lymphoblastic Leukemia - AIEOP-BFM ALL 2017
Status:
Recruiting
Trial end date:
2028-07-14
Target enrollment:
Participant gender:
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.