This phase II trial studies the effect of ASTX727 and dasatinib in treating patients with newly diagnosed Philadelphia chromosome or BCR-ABL positive chronic myeloid leukemia in chronic phase. Philadelphia chromosome positive and BCR-ABL positive are types of genetic mutations (changes). Chemotherapy drugs, such as ASTX727, 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. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. ASTX727 and dasatinib may help to control Philadelphia chromosome-positive chronic myeloid leukemia or BCR-ABL positive chronic myeloid leukemia in chronic phase.
Diagnosis of Philadelphia chromosome (Ph)-positive or BCR-ABL positive CML in early chronic phase CML (i.e., time from diagnosis ≤12 months). Except for hydroxyurea and/or 1 to 2 doses of cytarabine patients must have received no or minimal prior therapy, defined as < 1 month (30 days) of prior Food and Drug Administration (FDA) approved tyrosine kinase inhibitor (TKI)
Clonal evolution defined as the presence of additional chromosomal abnormalities other than the Ph chromosome has historically been included as a criterion for accelerated phase. However, patients with clonal evolution as the only criterion of accelerated phase have a significantly better prognosis, and when present at diagnosis may not impact the prognosis at all. Thus, patients with clonal evolution at diagnosis (early disease) and no other criteria for accelerated phase will be eligible for this study.
Eastern Cooperative Oncology Group (ECOG) performance of 0-2
Adequate end organ function, defined as the following: total bilirubin <1.5x ULN (unless secondary to Gilbert's disease, in which case should be < 2.5x ULN), SGPT <3x ULN, creatinine clearance ≥ 30mL/min calculated using modified Crokcroft-Gault.
New York Heart Association (NYHA) cardiac class 3-4 heart disease
Uncontrolled angina within 3 months
Diagnosed or suspected congenital long QT syndrome
Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes).
Single group
Dasatinib
DrugGiven PO
Decitabine and Cedazuridine
DrugGiven PO
Rate of molecular response 4 (MR4)
Will be estimated with 95% credible intervals. The association between molecular responses and demographic/ clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test.
Rate of MR4.5
Will be presented with 95% confidence intervals. The association between molecular responses and demographic/ clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test.
Major molecular response rate
Will be presented with 95% confidence intervals. The association between molecular responses and demographic/ clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test.
Treatment-free remission rate
Will be presented with 95% confidence intervals. The association between molecular responses and demographic/ clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test.
Time to progression
Survival time will be estimated using the Kaplan-Meier method. Patients who drop out of the study will be included in the time to event data as "censored data". The two-sided log-rank test will be used to assess the differences of time to events between groups.
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M.D. Anderson Cancer Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator
Astex Pharmaceuticals, Inc.
Collaborator
