TQ05105 Tablet for Myelofibrosis Treatment in Ruxolitinib-Resistant or Intolerant Patients

Myelofibrosis Clinical Trial

Official title:

A Phase Ib Study of TQ05105 Tablets for the Treatment of Intermediate and High Risk Myelofibrosis Refractory/Relapsed/Intolerant to Ruxolitinib

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06388759
• Other study ID #: TQ05105-Ib-03
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: August 1, 2022
• Est. completion date: December 2024

Study information

• Verified date: April 2024
• Source: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 9
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Myelofibrosis
• Primary Myelofibrosis

Intervention

Drug:
• TQ05105 Tablets
TQ05105 Tablets is a Janus kinase 1 (JAK1) and Janus kinase 2 (JAK2) Inhibitor

Locations

Country	Name	City	State
China	The First Hospital of Jilin University	Changchun	Jilin
China	Anhui Provincial Hospital	Hefei	Anhui
China	Shanghai Sixth People's Hospital	Shanghai	Shanghai
China	Union Hospital Tongji College Huazhong University of Science And Technology	Wuhan	Hubei
China	The First Affiliated Hospital of Wannan Medical College	Wuhu	Anhui
China	The Affiliated Hospital of Xuzhou Medical University	Xuzhou	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Spleen volume reduction (SVR35)=35% from baseline	The proportion of subjects with spleen volume reduction =35%from baseline at the end of treatment at week 24.	up to 24 weeks
Secondary	Optimum effective rate	The proportion of subjects with at least one spleen volume measurement of = 35% reduction against the baseline.	up to 120 weeks
Secondary	Onset time of splenic response	The time interval from the first administration to the date when the spleen volume was reduced by = 35 % from the baseline.	up to 120 weeks
Secondary	Duration of maintenance of spleen response (DoMSR) =35% reduction	The time between the date when the spleen volume reduction = 35% from baseline for the first time and the date when the spleen volume reduction < 35% from baseline.	up to 120 weeks
Secondary	Myeloproliferative neoplasm- Symptom Assessment Form- Total Symptom Score (MPN-SAF TSS) : = 50% Reduction from Baseline	The proportion of subjects whose total symptom score on the Myeloproliferative Neoplasia Symptom Assessment Form-Total Symptom Score (MPN-SAF TSS) scale decreased by at least 50% compared to baseline. MPN-SAF-TSS is an effective tool for evaluating the disease burden in patients with myeloproliferative neoplasms. A higher score indicates more severe symptoms in patients. Each symptom is scored according to its severity, ranging from no symptoms (0 points) to the most severe (10 points), with a total of 10 levels. The sum of the scores for these 10 symptoms constitutes the MPN-SAF-TSS score.	up to 24 weeks
Secondary	The total symptom score of MPN-SAF TSS decreased compared with baseline	The total symptom score of MPN-SAF TSS decreased compared with baseline.	up to 120 weeks
Secondary	Progression-free survival (PFS)	The time interval from the first medication to the date of the occurrence of any of the following events, whichever occurs first: (1) Spleen volume increased by=25% compared with the screening period ; (2) Death caused by any cause.	up to 120 weeks
Secondary	Leukemia free survival (LFS)	The time interval from the first medication to the occurrence of any of the following events, whichever comes first: ? The date on which the first bone marrow smear displays =20% blast cells; ? The first instance where the peripheral blood smear displays =20% blasts with an absolute blast count of =1×10^9/L, which persists for at least two weeks; ? Death caused by any reason.	up to 120 weeks
Secondary	Overall Survival (OS)	OS is defined as the time from the first time the subject received treatment to death due to any cause.	up to 120 weeks
Secondary	Incidence of adverse events (AEs)	All adverse medical events that occur after the subject receives the investigational drug may be manifested as symptoms, signs, disease, or laboratory abnormalities, but are not necessarily causally related to the investigational drug, evaluated according to the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0).	baseline up to 120 weeks
Secondary	Severity of AEs	All adverse medical events that occur after the subject receives the investigational drug may be manifested as symptoms, signs, disease, or laboratory abnormalities, but are not necessarily causally related to the investigational drug, evaluated according to the CTCAE v5.0.	baseline up to 120 weeks