Interfant-21 Treatment Protocol for Infants Under 1 Year With KMT2A-rearranged ALL or Mixed Phenotype Acute Leukemia

This study is a treatment protocol with blinatumomab for infants under 1 year old who are diagnosed with acute lymphoblastic leukemia with a specific unfavorable genetic alteration. The purpose of the study is to improve the outcome of this disease in infants.

All infants that are eligible for this study and for whom the parents/legal representatives give informed consent will be enrolled in this study. All patients will receive one cycle of blinatumomab on top of the standard treatment backbone after induction therapy. Medium risk patients, that respond well to the 1st cycle will be treated with a 2nd cycle of blinatumomab replacing one chemo course after consolidation therapy. If they do not respond well enough they will be treated according to the current treatment standard. Minimal residual disease will be used to determine the response to blinatumomab. High risk patients will be eligible for allogeneic stem cell transplantation after the first blinatumomab cycle if they are Minimal Residual Disease (MRD) negative (defined as \< 0.01%). Also medium risk patients with insufficient MRD response after induction or after the 1st cycle of blinatumomab will be allocated to high risk treatment and will be eligible for allogeneic stem cell transplantation.

Inclusion Criteria: 1. Patients with newly diagnosed B- precursor ALL or B-cell MPAL (single lineage) according to the WHO classification of tumours of haematopoietic and lymphoid tissues (revised 4th edition 2017), with KMT2A-rearrangement. 2. ≤ 365 days of age at the time of diagnosis of ALL. 3. Written informed consent of the parent(s) or other legally authorized guardian of the patient according to local law and regulations. Exclusion criteria for blinatumomab: 1. KMT2A-wildtype patients. 2. Multilineage MPAL 3. T-ALL. 4. Age \> 365 days at the time of diagnosis. 5. Down syndrome. 6. Relapsed ALL. 7. Treatment with systemic corticosteroids (equivalent prednisone \>10 mg/m2/day) for more than one week and/or any chemotherapeutic agent in the 4-week interval prior to diagnosis. Patients who received corticosteroids by aerosol are eligible for the study. If exclusion criteria for blinatumomab are met, the patient should be treated according to the protocol but without blinatumomab.