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

Inclusion Criteria:

1. Patients with newly diagnosed B- precursor acute lymphoblastic leukemia (ALL) or B-cell mixed phenotype acute leukemia (MPAL) according to the World HealthOrganization (WHO) classification of tumours of haematopoietic and lymphoid tissues (revised 4th edition 2017, with KMT2A-rearrangement.

2. ≤365 days of age at time of diagnosis of ALL

3. Written informed consent of the parents or other legally authorized guardian of thepatient according to local law and regulations.

Exclusion Criteria:

1. KMT2A-germline patients

2. T-ALL

3. Age > 365 days at the time of diagnosis

4. Relapsed ALL

5. Treatment with systemic corticosteroids (equivalent prednisone >10 mg/m2/day) formore than one week and/or any chemotherapeutic agent in the 4-week interval prior todiagnosis. Patients who received corticosteroids by aerosol are eligible for thestudy.

Additional exclusion criteria for blinatumomab:

1. CD19 negative B-precursor ALL at diagnosis

2. CNS involvement (CNS2/CNS3 status) at the EOI. Patients with CNS disease at the timeof diagnosis are eligible if CNS1 status is achieved prior to the start of the firstblinatumomab cycle (lumbar puncture at ~day 33 of induction).

3. Proven hypersensitivity to the active substance or any of the excipients inblinatumomab.

4. Patients who have received a live vaccine 28 days prior to blinatumomabadministration or plan to receive a live vaccine prior to B-cell recovery after thelast dose of blinatumomab.

If exclusion criteria for blinatumomab are met, the patient should be treated according to the protocol but without blinatumomab.