Overview
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
Description
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
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