Clinical trial NCT06453902: TGRX-678 Chinese Phase II in Chronic Myelogenous Leukemia (CML) Patients
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Chronic Myeloid Leukemia
Accelerated Phase CML
Lead sponsor: Shenzhen TargetRx, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Peking University People's Hospital
name: Henan Cancer Hospital
name: Nanfang Hospital, Southern Medical University
name: The First Affiliated Hospital of Soochow University
name: Chinese Academy of Medical Sciences
name: First Affiliated Hospital of Zhejiang University
name: Shenzhen Second People's Hospital
name: Ruijin Hospital
name: Shengjing Hospital
name: Tongji Medical College,Huazhong University of Science &Techonlogy
First posted: 2024-06-12
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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

Detailed 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 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

Primary outcomes:
measure: Major Hematologic Response (MaHR)
timeFrame: 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 outcomes:
measure: Cytogenetic Response
timeFrame: 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
measure: Major Molecular Response (MMR)
timeFrame: 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
measure: Time to Response (TTR)
timeFrame: 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
measure: Duration of Response (DOR)
timeFrame: 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
measure: Progression Free Survival (PFS)
timeFrame: 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
measure: Overall Survival (OS)
timeFrame: 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
measure: Treatment Emergent Adverse Event (TEAE)
timeFrame: Through completion of the study, an average of 3.5 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
Study officials:
affiliation: Peking University People's Hospital
name: Qian Jiang, MD
role: PRINCIPAL_INVESTIGATOR
References: