Interfant-21

Primary objective

The primary objective is to improve the outcome (in terms of event-free survival (EFS) as the primary endpoint) of newly diagnosed KMT2A-rearranged (KMT2A-r) infant acute lymphoblastic leukemia (ALL) compared with the historical results of the Interfant06 protocol.

Risk-strtification:

High risk (HR)
‐ age at diagnosis under 6 months AND WBC under 300 x 10*9/L and/or prednisone poor response

Medium risk (MR)
age over 6 months OR age under 6 months AND WBCunder 300 x 10*9/L AND prednisone good or unknown response
       Medium risk–low (MR-low)
       ‐ medium risk patients with MRD EOI under 0.05%
        Medium risk–high (MR-high)
        - medium risk patients with MRD EOI ≥ 0.05%

Medium risk patients allocated to High risk treatment
- medium risk patients not in CR at EOI
‐ medium risk patients with MRD over 0.01% post blinatumomab cycle 1

All patientts receive one cycle of blinatumomab following induction therapy. A second cycle of blinatumomab will replace MARMA in medium risk (MR) patients with good response after the first cycle of blinatumomab. All high risk (HR) patient and MR patients with insufficient MRD response will be eligible for allogeneic hematopoietic stem cell transplantation HSCT as soon as they become MRD negative or at least under 0.01%. HR patients and MR patients with insufficient MRD response will be eligible for experimental therapy, such as CAR T-cell therapy, which can be in a separate trial, as a bridge to HSCT .

• Patients with newly diagnosed B- precursor ALL or B-cell MPAL according to the WHO classification of tumours of haematopoietic and lymphoid tissues (revised 4th edition 2017), with KMT2A-rearrangement.
• Age up to 365 days atthe time of diagnosis of ALL.
• Written informed consent of the parents or other legally authorized guardian of the patient according to local law and regulations.

• KMT2A-germline patients.
• T-ALL.
• Age over 365 days at the time of diagnosis.
• Relapsed ALL.
• Treatment with systemic corticosteroids (equivalent prednisone over 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.