AIEOP-BFM ALL 2025 - International collaborative treatment protocol for children and adolescents with acute lymphoblastic leukemia

Prior treatment

• Pre-treatment with cytostatic drugs before ALL diagnosis. Exceptions include prior cytarabine treatment up to 100 mg/m² BSA for ≤ 2 days and/or a single dose of intrathecal triple therapy (Prednisolone, Cytarabine, and Methotrexate).
• Glucocorticoid pre-treatment with ≥ 1 mg/kg/d Prednisolone equivalent for more than two weeks during the last month before ALL diagnosis
• Sexually active adolescents not willing to use highly effective contraceptive method (pearl index <1) until 6 months (female) or 90 days (male) after end of anti-leukemic therapy
• B/SR: Live vaccine immunization within 2 weeks before start of Cons-Blina or Cons B-short
• ALL with other ABL class fusion if enrollment in a study specifically designed for these patients is possible or treatment with a tyrosine kinase inhibitor is planned

Other illness

• Underlying disease that does not allow treatment according to a standard of care ALL protocol (e.g. Severe congenital heart disease, Charcot-Marie-Tooth Syndrome, Ataxia-teleangiectasia…)
• Other condition (either pre-existing or related to leukemia biology as present at diagnosis) or circumstances that significantly conflict with the treatment according to a standard of care ALL protoco
• ALL diagnosed as second malignancy and preceding chemotherapy and/or radiotherapy
• B/SR: Hypersensitivity to the active substance of Blinatumomab or to any of its ingredients
• B/SR: Clinically relevant CNS pathology requiring treatment (e.g., unstable epilepsy)
• B/SR: Known infection with human immunodeficiency virus (HIV)
• B/SR: History or evidence of any other clinically significant disorder, condition or disease that, in the opinion of the investigator or the national coordinator, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion

Age

• Patients < 1 year of age with KMT2A-rearranged B-ALL if enrollment in a study specifically designed for these patients is possible

Other

• Ph+ (BCR::ABL1 or t(9;22)-positive) ALL
• Evidence of pregnancy or lactation period
• Participation in another clinical trial except for add-on trials within the scope of supportive care approved by the sponsor
• B/SR: MPAL meeting the criteria of a bilineal acute leukemia with a lymphoblastic and a separate non-lymphoblastic blast subset

• Newly diagnosed acute lymphoblastic leukemia (ALL)
• Newly diagnosed mixed phenotype acute leukemia (MPAL) meeting one of the following criteria: (1) biphenotypic with a dominant lymphatic lineage assignment, (2) bilineal either with a dominant lymphoblastic population or if another reasonable rationale exists to treat the patient with an ALL-based therapy regimen
• Age < 18 years (up to 17 years and 365 days) at the day of diagnosis
• Written informed consent to the screening procedure in the Master protocol
• B/SR: Newly diagnosed ALL with B-cell immunology or newly diagnosed MPAL meeting the criteria of a biphenotypic acute leukemia with a dominant B lineage assignment
• B/SR: Meeting the criteria for the B-ALL standard-risk group
• B/SR: Prior treatment with a SOC induction and the first part of consolidation therapy for low-risk B-ALL according to the AIEOP-BFM ALL 2024 Treatment Recommendations including (1) prednisone pre-phase and (2) induction Protocol IA’ and (3) start of Consolidation A. Medically justified deviations from the protocol are permitted
• B/SR: Written informed consent to the trial participation and transfer and processing of data. The assent of the child must be obtained, as appropriate to the age of the patient and/or based on local regulations