tgrx-678 chinese phase ii in chronic myelogenous leukemia (cml) patients

Conditions: Chronic Myeloid Leukemia; Accelerated Phase CML

Summary: a phase ii study evaluating the safety and efficacy of tgrx-678 in chronic myelogenous leukemia (cml) patients in accelerated phase (ap) and are relapsed or refractory from third-generation tyrosine kinase inhibitor (tki) treatment

this phase ii study is of single-arm, open-label and multi-center designs to study safety and efficacy profiles of tgrx-678 in cml-ap patients. patients need to have medical history of failing treatment(s) from third-generation tki drugs. patients with or without t315i mutation is enrolled.

Eligibility criteria:
inclusion criteria: * willing to consent * 18 years of age or above at time of screening; both sexes eligible * relapsed or refactory from 3rd-generation tyrosine kinase inhibitor (tki) treatment * for patients without t315i mutation, the patients must received 1st, 2nd and 3rd generation tki * for patients with t315i mutation, the patients much received olverembatinib or ponatinib treatment * diagnosis of cml-ap by bone marrow morphological test, molecular biology test or cytogenetic tests * ecog score \</=2 * minimum life expectancy of at least 3 months * adequate hematological indicators * adequate kidney function * adequate liver function * adequate coagulation function * adequate pancreatic function * adequate qtc interval as confirmed by electrocardiogram (ecg) test * negative pregnancy result at screening for female patients of child-bearing potential * willing to take contraceptive measure during the study (for male and female patients of child-bearing potential) exclusion criteria: * reception of tki treatment or presence of unrecovered tki treatment related non-hematological adverse events within 7 days of first dose * reception of other anti-tumor treatments * in need for immune suppressive treatment * usage of drugs associated with torsades de pointes within 1 months before screening * presence of other medical conditions that require using treatment that may have drug-drug interaction with the investigational drug * history of hemapoietic stem cell transplant * presence of active central nervous system conditions * cml-ap patients who already reached major hematological response * cml-ap patients who used to progress to blast phase (bp) * presence or having uncontrolled condition for cardiovascular diseases * history of any heart or cardiovascular conditions (except for patients with hypertension which is controlled by anti-hypertensive drugs, and blood pressure is controlled at no higher than 160/100 mmhg for 1 months before screening) * usage of any traditional chinese medicine indicated for anti-tumor purpose 2 weeks before first dose * severe hemorrhagic disease unrelated to cml * history of severe cardiovascular condition during past tki treatment for cml * history of pancreatic inflammation or alcohol abuse within 3 years before first dose * uncontrolled hypertriglyceridemia * presence of malabsorption or other conditions that may affect drug absorption * diagnosis of other primary malignant tumor within 5 years * reception of major surgery 14 days before first dose * presence of continuous or active infection (including hiv, hepatitis b, hepatitis c) * presence of other conditions that the investigators or medical monitor deem unfit for the study