City of Hope Medical Center
This phase I trial studies the side effects and best dose of asciminib when given together with intrathecal (IT) chemotherapy, dexamethasone, vincristine, and blinatumomab (asciminib-based induction therapy) in treating patients with newly diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Asciminib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as methotrexate and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Dexamethasone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Vincristine is in a class of medications called vinca alkaloids. It works by stopping cancer cells from growing and dividing and may kill them. Blinatumomab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Giving asciminib-based induction therapy may be safe, tolerable, and/or effective in treating patients with newly diagnosed Ph+ ALL.
PRIMARY OBJECTIVES: I. Evaluate the safety of asciminib as the tyrosine kinase inhibitor (TKI) backbone in a chemotherapy minimizing induction strategy (dexamethasone, vincristine, IT chemotherapy, blinatumomab). II. Determine the recommended phase 2 dose (RP2D) of asciminib induction therapy as the TKI backbone in a reduced intensity strategy for the treatment of Ph+ ALL. SECONDARY OBJECTIVES: I. To evaluate the safety and tolerability of an asciminib-based therapy for post-dose limiting toxicity (DLT) cycles. II. To evaluate the complete molecular response (CMR) rate after 1 and 3 cycle…
Inclusion Criteria: * Documented informed consent of the participant and/or legally authorized representative * Newly diagnosed Ph+ or BCR-ABL1-positive ALL, as defined by the 2025 National Comprehensive Cancer Network (NCCN) guidelines * Age: ≥ 18 years * Eastern Cooperative Oncology Group (ECOG) ≤ 2 * Total bilirubin ≤ 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease) * Aspartate aminotransferase (AST) ≤ 3.0 x ULN * Alanine aminotransferase (ALT) ≤ 3.0 x ULN * Serum creatinine \< 1.5 mg/dL * Left ventricular ejection fraction (LVEF) ≥ 50% * Note: To be performed within 28…
Given PO
Undergo blood and CSF sample collection
Given IV
Undergo bone marrow aspiration
Given IT
Given IT
Given PO
Undergo ECHO
Given IT
Given IV