Recruiting
Phase 1/2
A Clinical Trial of TQ05105 Tablets Combined With TQB3617 Capsules in the Treatment of Myelofibrosis (MF)
Condition(s) studied
Myelofibrosis
Investigational drug(s) / intervention(s)
TQ05105 Tablets: TQ05105 Tablets is a Janus kinase 1 (JAK1) and Janus kinase 2 (JAK2) Inhibitor.
TQB3617 Capsules: TQB3617 Capsules is a Bromodomain and Extra-Terminal (BET) Inhibitor
Study summary
This is an open, single-arm, multi-center clinical study designed to evaluate the efficacy and safety of TQ05105 Tablets combined with TQB3617 Capsules in patients with intermediate- and high-risk Myelofibrosis.
Eligibility
Inclusion Criteria:
* Voluntary and signed informed consent, good compliance.
* Age: 18 or above (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.
* Within 7 days before the first administration, the symptom score of myeloproliferative neoplasms should meet certain requirements.
* Patients with poor efficacy of JAK inhibitors (for phase Ib and phase II cohort 2, cohort 3)
* Patients who had not received JAK inhibitor treatment (for phase II cohort 1).
* 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 BET inhibitors combined with JAK inhibitor;
* Patients who have previously undergone splenectomy, or received splenic radiotherapy within 6 months before the first administration;
* Use of any MF medications, any immunomodulators, any immunosuppressive agents, within 2 weeks prior to first administration (There are separate withdrawal requirements for hydroxyurea, JAK inhibitors, androgen drugs, erythropoietin, long-acting recombinant interferon-α, etc.);
* 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;
* 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, or active Corona Virus Disease 2019 (COVID-19) infection;
* Patients with grade III or above congestive heart failure, unstable angina pectoris or myocardial infarction, or arrhythmia requiring treatment, or QT interval prolongation within 6 months before the first administration;
* 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;
* 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 (except JAK inhibitor-related clinical trials).
* 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 outcome measure(s)
- Maximal tolerance dose (MTD) — Up to 2 years.
If dose limiting toxicity (DLT) occurs in 2 or more subjects in a given dose group, the dose level in the previous dose group is considered MTD.
- Recommended phase II dose (RP2D) — Up to 2 years
The RP2D is defined as the lower dose level to MTD based on the safety profile.
- ≥35% reduction in spleen volume (SVR35) — Up to 24 weeks
The proportion of subjects with a ≥35% reduction in spleen volume from baseline at the end of treatment at week 24.
Trial sites (22)
| Facility | City | Region | Status |
| Guangdong Provincial People's Hospital |
Guangzhou |
Guangdong |
Not Yet Recruiting |
| Guangxi Zhuang Autonomous Region People's Hospital |
Nanning |
Guangxi |
Not Yet Recruiting |
| Cangzhou People's Hosipital |
Cangzhou |
Hebei |
Not Yet Recruiting |
| Affiliated Hospital of Chengde Medical College |
Chengde |
Hebei |
Not Yet Recruiting |
| North China of Science and Technology University Affiliated Hospital |
Tangshan |
Hebei |
Not Yet Recruiting |
| Xingtai People's Hospital |
Xingtai |
Hebei |
Not Yet Recruiting |
| The First Hospital of Harbin |
Harbin |
Heilongjiang |
Not Yet Recruiting |
| Henan Cancer Hospital |
Zhengzhou |
Henan |
Not Yet Recruiting |
| Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology |
Wuhan |
Hubei |
Not Yet Recruiting |
| Union Hospital Tongji College Huazhong Unizersity of Science And Technology |
Wuhan |
Hubei |
Not Yet Recruiting |
| Wuhan University Zhongnan Hospital |
Wuhan |
Hubei |
Not Yet Recruiting |
| The Affiliated Hospital of Inner Mongolia Medical University |
Hohhot |
Inner Mongolia |
Not Yet Recruiting |
| The Public Hospital of Wuxi |
Wuxi |
Jiangsu |
Not Yet Recruiting |
| The First Hospital of Jilin University |
Changchun |
Jilin |
Not Yet Recruiting |
| Xi 'An Jiaotong University Second Affiliated Hospital |
Xi'an |
Shaanxi |
Not Yet Recruiting |
| Tai'an City Central Hospital |
Tai’an |
Shandong |
Not Yet Recruiting |
| Central Hospital Of Minhang District, Shanghai |
Shanghai |
Shanghai Municipality |
Not Yet Recruiting |
| Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine |
Shanghai |
Shanghai Municipality |
Recruiting |
| Shanghai Sixth People's Hospital |
Shanghai |
Shanghai Municipality |
Recruiting |
| Heping Hospital Affiliated to Changzhi Medical College |
Changzhi |
Shanxi |
Not Yet Recruiting |
| People's Hospital of Tianjin City |
Tianjin |
Tianjin Municipality |
Not Yet Recruiting |
| The First Affiliated Hospital of Xinjiang Medical University |
Ürümqi |
Xinjiang |
Not Yet Recruiting |
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