TGRX-678 US Phase I for Subjects with Refractory or Advanced Chronic Myelogenous Leukemia

Summary

The purpose of this single-arm, open-label, dose escalation + cohort expansion study is to evaluate the safety, tolerability, pharmacokinetic and preliminary efficacy of TGRX-678 in Chronic Myelogenous Leukemia patients who had failure with or are intolerant to TKI treatments.

Eligibility

Inclusion Criteria:

* Willing to participate in the study with informed consent;
* At least 18 years of age at the time of screening;
* Any sex;
* Diagnosis of CML-CPduring the screening period;
* Intolerant or resistant to TKI treatments;
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;
* Adequate Absolute neutrophil count (ANC), hemoglobin and platelets levels;
* Adequate renal and liver function;
* Normal corrected QT (QTcF) interval as indicated by electrocardiogram (ECG) screening results;
* Negative blood pregnancy test results for female patients of childbearing potential.
* Willing to take highly effective contraceptive measures throughout the trial and for 6 months after last dose of investigational drug for female subjects of child-bearing potential or male subject with female partner of child-bearing potential.

Exclusion Criteria:

* Exposure to other antineoplastic therapies prior to study enrollment;
* Exposure to other investigational agent(s) within 14 days of initiating TGRX-678 therapy;
* Ongoing toxicity from prior therapy greater than grade 1 by CTCAE v. 3 (except alopecia);
* Hematopoietic cell transplantation \< 60 days prior to the first dose;
* Evidence of graft versus host disease (GVHD), whether or not requiring immunosuppressive therapy;
* Concomitant immunosuppressive therapy (other than short-term corticosteroid treatment);
* Exposure to drugs related to torsade de pointes;
* Cytological or pathological diagnosis of active central nervous system disorder;
* Significant or uncontrolled cardiovascular diseases as defined in the full clinical protocol;
* Having long QT syndrome, or with family history of idiopathic sudden death or congenital long QT syndrome;
* Uncontrolled hypertension;
* Receipt of Traditional Chinese medication or herbal preparations indicated for anti-cancer purposes within 2 weeks prior to the first dose;
* Severe hemorrhagic disorders unrelated to CML;
* History of pancreatitis;
* History of excessive alcohol use;
* History of elevation in amylase or lipase within 1 year;
* Have Grade 2 or worse interstitial lung disease or interstitial pneumonitis within 4 weeks prior to Screening;
* Uncontrolled hypertriglyceridemia;
* Malabsorption syndrome or other illness that could affect oral absorption.
* Diagnosis of another primary malignancy in the past 3 years;
* Reception of major surgery within 14 days prior to the first dose;
* Active infections that require systemic treatment or other severe infections within 14 days prior to enrollment;
* Known human immunodeficiency virus (HIV) positive; acute or chronic liver disease (including chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections);
* Have received or will receive a COVID-19 vaccine within 14 days of study enrollment;
* Have a positive reverse transcriptase polymerase chain reaction (RT-PCR) test result for SARS-CoV-2 within 2 weeks prior to Screening;
* Pregnant or breastfeeding female;
* Female patient of child-bearing potential or male patient who have female partners of child-bearing potential that is unable or unwilling to take highly effective contraceptive measures during the trial and for 6 months after last dose of investigational drug;
* Significant organ dysfunction that could compromise the patient's safety or the evaluation of the drug's safety in the opinion of the investigator or the medical monitor;
* Any condition makes participation in this trial inappropriate in the opinion of the investigator or medical monitor;

Conditions2

Locations2 sites

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