Philadelphia Chromosome Negative, BCR-ABL1 Positive Chronic Myelogenous Leukemia Clinical Trial
Official title:
Phase II Study of Dual Targeting of BCR-ABL1 by Adding the Allosteric Inhibitor ABL001 in Patients With Chronic Myeloid Leukemia (CML) and Minimal Residual Disease (MRD) While on Therapy With Tyrosine Kinase Inhibitors
This phase II trial studies how well ABL001 works in treating patients with chronic myeloid leukemia who are on therapy with tyrosine kinase inhibitor. ABL001 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving ABL001 and tyrosine kinase inhibitor together may work better than tyrosine kinase inhibitor alone in treating patients with chronic myeloid leukemia.
PRIMARY OBJECTIVE: I. To determine the clinical activity of the combination of asciminib (ABL001) and a tyrosine kinase inhibitor (TKI) in patients with chronic myeloid leukemia (CML) in complete cytogenetic response (CCyR) but detectable BCR-ABL1 transcript. SECONDARY OBJECTIVES: I. To determine the effect of the combination of ABL001 and TKI on the rate of mismatch repair (MR)4, MR4.5, and sustained MR4.5. II. To investigate treatment-free remission after at least 2 years of sustained deep molecular remission. III. To determine the safety of the combination of asciminib and tyrosine kinase inhibitors. IV. To determine the event-free survival (EFS), survival free from transformation to accelerated and blast phase (TFS), and overall survival (OS). EXPLORATORY OBJECTIVES: I. To determine the rate of minimal residual disease (MRD) clearance using droplet digital polymerase chain reaction (ddPCR) detecting the BCR-ABL1 fusion transcript. II. To determine the effect of therapy on quiescent leukemic Philadelphia chromosome positive (Ph+) stem cells (CFSEmax/CD34+). III. To determine the effect of this combination on mutations in ABL1 and mutations in clonal hematopoiesis of indeterminate potential (CHIP)-associated genes using molecular barcode sequencing. IV. To determine the effect of therapy on bone marrow progenitors in clonogenic assays. V. To describe immune effects of the combination of TKI and ABL001. VI. To describe patient reported outcomes (PRO) using the MD Anderson Symptom Inventory (MDASI)-CML instrument. OUTLINE: Patients receive asciminib orally (PO) twice daily (BID) for up to 36 months while receiving standard of care dasatinib or nilotinib in the absence of disease progression or unacceptable toxicity. Patients may continue to receive asciminib after 36 months at the discretion of investigator. After completion of study treatment, patients are followed up every 4-8 weeks for 6 months and then every 3-6 months thereafter. ;
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