Adding Asciminib to Usual Treatment for Adults With Newly Diagnosed Philadelphia Chromosome Positive (Ph+) Acute Lymphoblastic Leukemia

PRIMARY OBJECTIVES: I. To assess the rate of major molecular remission (MMR) by polymerase chain reaction (PCR) for BCR-ABL at day 85 in newly diagnosed participants with Philadelphia-chromosome positive Ph+ acute lymphoblastic leukemia (ALL) treated with asciminib, dasatinib and prednisone. SECONDARY OBJECTIVES: I. To estimate the rate of complete remission (with and without complete count recovery, CR/CRi) at day 85 in this participant population. II. To describe disease-free survival (DFS) in this participant population. III. To estimate overall survival (OS) in this participant population. IV. To estimate the frequency and severity of toxicities in this participant population. V. To estimate the rate of measurable residual disease remission by flow cytometry (MRD Flow) at day 85 in this participant population. VI. To compare rates of MMR by PCR and MRD flow remission in this participant population. VII. Among participants who achieve MMR, to estimate the cumulative incidence of relapse from MMR in this participant population. VIII. To describe attainment and failure of MR3.0, MR4.0 and MR4.5 at day 85 in this participant population. IX. To estimate the rate of complete remission with undetectable MRD levels by flow cytometry (MRDundetectable CR) in this participant population. X. To estimate duration of MMR in this participant population. XI. To estimate duration of MR4.0 in this participant population. XII. To estimate time to treatment failure in this participant population. XIII. To describe event-free survival (EFS) in this participant population. TRANSLATIONAL MEDICINE OBJECTIVES: I. To evaluate and describe the genes and pathways associated with response (molecular response) to therapy. II. To describe the spectrum of mutations observed, and the timing of their emergence, in resistant/relapse samples. III. To bank specimens for future correlative studies. OUTLINE: Patients will have their phase of treatment determined by their responses tested by blood and bone marrow tests. PHASE 1 TREATMENT (INDUCTION): Phase 1 treatment may last up to 12 weeks. Patients will start with 4 weeks of treatment. Patients will receive Asciminib every day with a combination of other drugs. After 4 weeks of Phase 1 treatment, patients will be testing to see how the leukemia is responding. If There are no more signs of leukemia, the patients will receive 8 more weeks of Phase 1 treatment. if there are still signs of leukemia, patients will receive 4 more weeks of Phase 1 treatment and then will be tested again. If there are no signs of leukemia, they will receive 4 more weeks of Phase 1 treatment for a total of 12 weeks. If there are no signs of leukemia, patients will start Phase 2 treatment. If there are still signs of leukemia, the patients will start Re-induction treatment. Re-Induction treatment may last up to 12 weeks. Patients will start with 6 weeks of treatment. Patients will receive Blinatumomab every day for 28 days and Dasatinib every day for 42 days. After weeks of treatment, patients are tested and if there are no signs of leukemia, patients will start Phase 2 treatment. If there are still signs of leukemia, patients will repeat 6 weeks of Re-induction treatment. After repeating 6 weeks of Re-induction treatment if there are no signs of leukemia, patients will start Phase 2 treatment. If there are still signs of leukemia, patients will stop treatment in the study. PHASE 2 TREATMENT (POST-REMISSION): Phase 2 treatment will last up to 18 weeks. Patients will receive treatment in cycles of 42 days. There are 3 cycles of Phase 2 treatment. Patients will receive Blinatumomab every day for days 1-28 of each cycle and Dasatinib every day of each cycle. After Phase 2 treatment, patients will be tested. If there are no signs of leukemia, patients will start Phase 3 treatment. If there are signs of leukemia, patients will stop treatment in the study. PHASE 3 TREATMENT (MAINTENANCE): Patients will receive maintenance treatment for as long as it helps them. Phase 3 Treatment is given in 28-day cycles. Patients will receive Asciminib every day of each cycle, for up to five years from the time they started the study. Patients will take Dastinib every day of each cycle for as long as it helps them and Prednisone days 1-5 of each cycle for 18 cycles. Patients will stop treatment if the leukemia comes back or if side effects become too severe. After completion of study treatment, patients are followed up on every 3 months for the first two years, and every 6 months until five years after treatment ends.