Clinical Trial Finder

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

• - 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

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.

Arms

Experimental: Experimental: TGRX-678

All patients with CML-AP to be treated with TGRX-678. Patients with T315I mutation or without T315I mutation will be assigned into separate cohorts for evaluation

Interventions

Drug: - TGRX-678

All patients will be given TGRX-678 240 mg once daily. TGRX-678 is to be taken orally