Interfant-21: behandeling voor kinderen jonger dan 1 jaar met acute lymfatische leukemie met een afwijking in het KMT2A gen

Compared to older children with acute lymphoblastic leukemia (ALL), infants with KMT2A-rearranged ALL have dismal outcome with a 3-year event free survival (EFS) of less than 40%, despite more intensive chemotherapy.

Solution

New upfront-targeted therapies are needed in this infant population

Research direction

Blinatumomab is new targeted therapy directed against CD19, and is already approved for older children with relapse CD19 positive ALL.

Aim

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

Plan of investigation

International multicenter open-label non-randomized phase 3 clinical trial conducted in the Interfant network.

The Interfant-21 protocol will implement several major changes to the Interfant06 backbone:
 
The following changes are considered improvements of standard of care:

• Less stringent adaptation of age-based dose reduction guidelines
• Allocation to lymphoid or myeloid consolidation therapy, based upon end of induction minimal residual disease (MRD) in medium risk patients
• 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 < 0.01%
• HR patients and medium risk (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.

The study also contains an IMP as detailed below:

• One cycle of blinatumomab following induction in all patients
• A second cycle of blinatumomab will replace MARMA in MR patients with good response after the first cycle of blinatumomab

Expected outcome

With 160 patients, the study will achieve 81% power to detect an absolute difference in EFS of 11% over the historical 3-year EFS of 40% observed on the Interfant06 protocol.

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