ABL001 Combo Therapy for Leukemia

This trial tests a new drug combination for certain types of leukemia, specifically B-cell Acute Lymphoblastic Leukemia and Chronic Myeloid Leukemia, both with specific genetic markers (BCR-ABL positive). The study aims to determine if combining ABL001 (Asciminib or Scemblix) with dasatinib (Sprycel), prednisone, and later adding blinatumomab can improve treatment outcomes. The trial seeks participants with these types of leukemia who have not received standard chemotherapy or have conditions that make intense chemotherapy unsuitable. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

The trial requires that certain medications be stopped before starting the study. Specifically, any TKI therapy must be discontinued for 5 half-lives before starting the trial, and other chemotherapy must be stopped 2 weeks prior, except for certain exceptions like steroids. Additionally, medications that strongly affect certain liver enzymes should be stopped unless medically necessary, in which case a review with the study investigator is needed.

Research has shown that ABL001 combined with dasatinib, prednisone, and blinatumomab can be safely managed in patients with Philadelphia chromosome positive (Ph+) acute leukemia. The combination of dasatinib and blinatumomab has yielded promising results, with good overall survival rates in previous studies. Although limited data exists on using ABL001 with dasatinib and prednisone in adults with Ph+ B-ALL or CML, these drugs have been well-studied in various combinations.

Dasatinib, a key drug in this mix, is already effective for Ph+ acute leukemia. However, some patients may develop resistance to it. Adding blinatumomab addresses this issue, as it has improved survival chances for older patients.

Researchers are excited about the ABL001 combo therapy for leukemia because it combines several potent treatments in a novel way. Unlike standard therapies, this trial includes Blinatumomab, which is given as a continuous infusion and targets specific proteins on cancer cells, potentially improving precision in treatment. Additionally, ABL001 is an oral medication, which could make it more convenient for patients compared to some intravenous treatments. Together, these features might provide a new approach to managing leukemia, potentially leading to improved outcomes for patients.

Research has shown that dasatinib effectively treats Philadelphia chromosome-positive acute leukemia, but some patients may stop responding to it. In this trial, participants will receive a combination of dasatinib with two other drugs, asciminib (ABL001) and prednisone, which studies suggest might help when resistance occurs. Additionally, blinatumomab, a type of antibody therapy, will be added to the treatment regimen starting from cycle 2, potentially enhancing effectiveness. Although specific data on using all these drugs together is limited, early research indicates that this combination might work better than using each drug individually.¹²³⁵⁶