TGRX-678 Chinese Phase II in Chronic Myelogenous Leukemia (CML) Patients

Chronic Myeloid Leukemia Clinical Trial

Official title:

A Single-arm, Open-label, Multi-center Phase II Study Evaluating Efficacy and Safety of TGRX-678 in CML-AP Patients Relapsed or Refractory From 3rd-generation TKI Treatment

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06453902
• Other study ID #: TGRX-678-2001
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 15, 2024
• Est. completion date: December 15, 2027

Study information

• Verified date: June 2024
• Source: Shenzhen TargetRx, Inc.
• Contact: Yingkun Lu
• Phone: 18602219981
• Email: yingkun.lv[@]tjrbiosciences.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: December 15, 2027
• Est. primary completion date: July 15, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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

Related Conditions & MeSH terms

• Chronic Myeloid Leukemia
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Intervention

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

Locations

Country	Name	City	State
China	Peking University People's Hospital	Beijing	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Shenzhen TargetRx, Inc.	Peking University People's Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Major Hematologic Response (MaHR)	Number of patients who reached, and rate of occurence of major hematologic response, including those who reached complete hematologic response (CHR) or no evidence of leukemia (NEL). CHR and NEL are defined per China national treatment guideline for CML (ver. 2022). Indicators for hematologic responses will be obtained via peripheral blood tests.	At screening, on Day 1 of every treatment cycle (each cycle is 28 days) and at end of treatment; average of study duration is 3.5 years
Secondary	Cytogenetic Response	Number of patients who reached, and rate of occurence of cytogenetic response, including those with major cytogenetic response (MCyR) or complete cytogenetic response (CCyR). Cytogenetic responses are defined per China national treatment guideline for CML (ver. 2022). Indicators for cytogenetic responses will be obtained via bone marrow biopsy.	At screening, on Day 1 of cycle 2, cycle 4 and every 3 cycles afterwards of the treatment cycle (each cycle is 28 days) and at the end of treatment; average of study duration is 3.5 years
Secondary	Major Molecular Response (MMR)	Number of patients who reached, and rate of occurence of MMR. Cytogenetic response is defined per China national treatment guideline for CML (ver. 2022). Indicators for molecular responses will be obtained via genetic testing on transcript levels of BCR-ABL gene.	At screening, on Day 1 of cycle 2, cycle 4 and every 3 cycles afterwards of the treatment cycle (each cycle is 28 days) and at the end of treatment; average of study duration is 3.5 years
Secondary	Time to Response (TTR)	TTR defined by the time from the start of treatment to the first efficacy response; TTR as evaluated by investigator	At screening, on Day 1 of cycle 2, cycle 4 and every 3 cycles afterwards of the treatment cycle (each cycle is 28 days) and at the end of treatment; average of study duration is 3.5 years
Secondary	Duration of Response (DOR)	DOR defined as the duration from first occurence of treatment response to progressive disease/relapse; DOR as evaluated by investigator	At screening, on Day 1 of cycle 2, cycle 4 and every 3 cycles afterwards of the treatment cycle (each cycle is 28 days) and at the end of treatment; average of study duration is 3.5 years
Secondary	Progression Free Survival (PFS)	PFS defined as the time from enrollment to progressive disease or death of any cause; PFS as evaluated by investigator.	At screening, on Day 1 of cycle 2, cycle 4 and every 3 cycles afterwards of the treatment cycle (each cycle is 28 days) and at the end of treatment; average of study duration is 3.5 years
Secondary	Overall Survival (OS)	OS defined as the time from enrollment to death of any cause; OS as evaluated by investigator	At screening, on Day 1 of cycle 2, cycle 4 and every 3 cycles afterwards of the treatment cycle (each cycle is 28 days) and at the end of treatment; average of study duration is 3.5 years
Secondary	Treatment Emergent Adverse Event (TEAE)	To record and analyse the occurence and frequency of adverse events during the study	Through completion of the study, an average of 3.5 years