The purpose of this study is to test whether it is feasible to include the study drugs, blinatumomab and venetoclax, in the chemotherapy regimen used to treat infants with KMT2A- ALL. The study will test the good and bad effects of the study drugs. Blinatumomab and venetoclax in combination with standard chemotherapy could help treat the leukemia.

Venetoclax and Blinatumomab are both investigational drugs, which means they are not approved by the U.S. Food and Drug Administration (FDA). 
   
Steroid Prephase:
Treatment on this part of the study takes about 7 - 10 days. 

Safety Phase:
Treatments for patients with KMT2A-R leukemia during the Safety Phase. This part of the study takes about 2.5 years. It is divided into 7 phases: Induction, Blinatumomab Block 1, Consolidation, MARMA, Blinatumomab Block 2, Delayed Intensification, and Maintenance. The study team will discuss treatment doses with each individual participant.

The total treatment lasts approximately 2.5 years from diagnosis. Participants will be monitored closely throughout therapy to monitor for possible side effects. After finishing treatment, the doctor will continue to follow the participant's condition for about 5 years after entering this study. This means they will keep seeing the doctor for 3 years after treatment.

Expansion Phase:
Treatment on this part of the study takes about 2.5 years. It is divided into 7 phases: Induction, Blinatumomab Block 1, Consolidation, MARMA, Blinatumomab Block 2, Delayed Intensification, and Maintenance. 

We will use a computer to assign participants to one of the study groups. This process is called “randomization.

Participants randomized to Arm A will receive these 7 phases of therapy without the addition of venetoclax. Participants randomized to Arm B will receive these 7 phases of therapy with the addition of venetoclax.

The total treatment lasts approximately 2.5 years from diagnosis. After finishing treatment, the doctor will continue to follow the participant's condition for about 5 years after entering this study. This means they will keep seeing the doctor for 3 years after treatment. 

Arm C:
There is only one group on this part of the study and everyone will follow the same treatment plan. The treatment on this part of the study takes about 2.5 years. It is divided into 8 phases: Induction, Blinatumomab Block 1, Consolidation, Interim Maintenance I, Blinatumomab Block 2, Delayed Intensification, Interim Maintenance II, and Maintenance

The total treatment lasts approximately 2.5 years from diagnosis. Participants will be monitored closely throughout therapy to monitor for possible side effects. After finishing treatment, the doctor will continue to follow the participant's condition for about 5 years after entering this study. This means they will keep seeing the doctor for 3 years after treatment.