Clinical trial NCT06388759: TQ05105 Tablet for Myelofibrosis Treatment in Ruxolitinib-Resistant or Intolerant Patients
Official title: A Phase Ib Study of TQ05105 Tablets for the Treatment of Intermediate and High Risk Myelofibrosis Refractory/Relapsed/Intolerant to Ruxolitinib
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Myelofibrosis
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-04-29
Enrollment: 9
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: This is an open, single-arm, multi-center clinical study designed to evaluate the efficacy of TQ05105 Tablets in patients with intermediate-risk and high-risk myelofibrosis.


Eligibility criteria: Inclusion Criteria:

* Subjects voluntarily participated in this study, signed informed consent forms, and demonstrated good compliance；
* Age: 18 or older (when signing the informed consent form); Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 2; Life expectancy ≥ 24 weeks;
* Patients diagnosed with Primary myelofibrosis (PMF), post polycythemia vera myelofibrosis (post-PV MF), or post essential thrombocythemia myelofibrosis (post-ET MF);
* According to the dynamic international prognostic scoring system (DIPSS), patients with intermediate or high risk of bone marrow fibrosis were evaluated;
* Patients with poor efficacy or intolerant of Ruxolitinib;
* Spleen enlargement;
* Peripheral blood primary cells and bone marrow primary cells were ≤10%;
* No growth factor, colony stimulating factor, thrombopoietin or platelet transfusion was received within 2 weeks before the examination, and the blood routine indexes met the requirements within 7 days before the first administration;
* The Main organ function is normal;
* Men and women of childbearing age should agree to use contraceptive measures (such as intrauterine devices, contraceptives, or condoms) during the study period and within 6 months after the end of the study. Serum human chorionic gonadotrophin（HCG）test is not negative within 7 days before the first administration and must be non-lactating patients.

Exclusion Criteria:

* Patients who have previously received allogeneic stem cell transplantation, or received autologous stem cell transplantation within 3 months before the first administration, or recently planned stem cell transplantation;
* Previous treatment with JAK inhibitors(except ruxolitinib);
* Patients who have previously undergone splenectomy, or received splenic radiotherapy within 6 months before the first administration;
* Other malignancies within 3 years prior to first administration or currently present;
* Patients with multiple factors (such as inability to swallow, postoperative gastrointestinal resection, acute and chronic diarrhea, intestinal obstruction, etc.) affecting oral or absorption of drugs;
* The non-hematological toxicity caused by previous treatment did not return to grade≤1;
* Major surgical treatment or significant traumatic injury within 4 weeks prior to first administration;
* Presence of congenital bleeding disorder and congenital coagulopathy;
* Patients who had arterial/venous thrombosis events within 6 months before the first administration;
* Have a history of mental drug abuse, or have a mental disorder;
* Active or uncontrolled severe infection;
* Active hepatitis B virus (HBV) infection, or hepatitis C virus (HCV) infection and HCV RNA positive;
* Patients with ≥ grade 2 myocardial ischemia or myocardial infarction, arrhythmia, QT interval prolongation and ≥ grade 2 congestive heart failure;
* Unsatisfactory blood pressure control despite standard therapy;
* Patients with renal failure requiring hemodialysis or peritoneal dialysis;
* Patients newly diagnosed with pulmonary interstitial fibrosis or drug-related interstitial lung disease within 3 months before the first administration;
* Patients with a history of immunodeficiency disease or organ transplantation;
* Patients with epilepsy requiring treatment;
* Use of any MF medications, any immunomodulators, androgens, any immunosuppressive agents, erythropoietin, aspirin \> 100 mg/day within 2 weeks prior to first administration;
* Patients who have received Chinese patent medicines with anti-tumor indications specified in the approved drug package insert of China National Medical Products Administration (NMPA) within 2 weeks before the first administration;
* Patients with uncontrolled pleural effusion, pericardial effusion or ascites;
* There was a history of attenuated live vaccine inoculation within 4 weeks before the first administration, or attenuated live vaccine inoculation was planned during the study period;
* People with known hypersensitivity to the study drug and excipients;
* Patients diagnosed as active autoimmune diseases within 2 years before the first administration;
* Those who participated in and used other anti-tumor clinical trial drugs within 4 weeks before the first administration;
* According to the judgment of the investigators, some situations seriously endanger the safety of the subjects or affect the subjects to complete the study.

Primary outcomes:
measure: Spleen volume reduction (SVR35)≥35% from baseline
timeFrame: up to 24 weeks
Secondary outcomes:
measure: Optimum effective rate
timeFrame: up to 120 weeks
measure: Onset time of splenic response
timeFrame: up to 120 weeks
measure: Duration of maintenance of spleen response (DoMSR) ≥35% reduction
timeFrame: up to 120 weeks
measure: Myeloproliferative neoplasm- Symptom Assessment Form- Total Symptom Score (MPN-SAF TSS) : ≥ 50% Reduction from Baseline
timeFrame: up to 24 weeks
measure: The total symptom score of MPN-SAF TSS decreased compared with baseline
timeFrame: up to 120 weeks
measure: Progression-free survival (PFS)
timeFrame: up to 120 weeks
measure: Leukemia free survival (LFS)
timeFrame: up to 120 weeks
measure: Overall Survival (OS)
timeFrame: up to 120 weeks
measure: Incidence of adverse events (AEs)
timeFrame: baseline up to 120 weeks
measure: Severity of AEs
timeFrame: baseline up to 120 weeks
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Wuhu
country: China
facility: The First Affiliated Hospital of Wannan Medical College
state: Anhui
city: Wuhan
country: China
facility: Union Hospital Tongji College Huazhong University of Science And Technology
state: Hubei
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Shanghai
country: China
facility: Shanghai Sixth People's Hospital
state: Shanghai
Study officials:
References: