A Clinical Trial of TQ05105 Tablets Combined With TQB3617 Capsules in the Treatment of Myelofibrosis (MF)

Официальное название

A Phase Ib/II Clinical Trial of TQ05105 Tablets Combined With TQB3617 Capsules in the Treatment of Intermediate- and High-risk Myelofibrosis

Обзор

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.

Вмешательства

• Препарат TQ05105 Tablets
  TQ05105 Tablets is a Janus kinase 1 (JAK1) and Janus kinase 2 (JAK2) Inhibitor.
• Препарат TQB3617 Capsules
  TQB3617 Capsules is a Bromodomain and Extra-Terminal (BET) Inhibitor

Первичные конечные точки

• Maximal tolerance dose (MTD) [Срок оценки: Up to 2 years.]
• Recommended phase II dose (RP2D) [Срок оценки: Up to 2 years]
• ≥35% reduction in spleen volume (SVR35) [Срок оценки: Up to 24 weeks]

Вторичные конечные точки (12)

• SVR35 [Срок оценки: Up to 120 weeks]
• Optimum effective rate [Срок оценки: Up to 120 weeks]
• Onset time of splenic response [Срок оценки: Up to 120 weeks]
• Duration of maintenance of at least 35% Reduction in Spleen Volume (DoMSR) [Срок оценки: Up to 120 weeks]
• Myeloproliferative neoplasm - Symptom Assessment Form - Total Symptom Score (MPN-SAF TSS) [Срок оценки: Up to 60 weeks]
• MPN-SAF TSS change [Срок оценки: Up to 120 weeks]
• Variant allele frequency (VAF) [Срок оценки: Up to 48 weeks]
• The proportion of subjects with gene mutation achieving SVR35 [Срок оценки: Up to 48 weeks]
• The proportion of subjects with gene mutation whose MPN-SAF TSS scale decreased by ≥ 50% [Срок оценки: Up to 48 weeks.]
• Progression-free survival (PFS) [Срок оценки: Up to 120 weeks]
• Leukemia free survival (LFS) [Срок оценки: Up to 120 weeks]
• Overall Survival (OS) [Срок оценки: Up to 120 weeks]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 22 центра

• Guangdong Provincial People's Hospital — Гуанчжоу
• Guangxi Zhuang Autonomous Region People's Hospital — Nanning
• Cangzhou People's Hosipital — Cangzhou
• Affiliated Hospital of Chengde Medical College — Chengde
• North China of Science and Technology University Affiliated Hospital — Tangshan
• Xingtai People's Hospital — Xingtai
• The First Hospital of Harbin — Харбин
• Henan Cancer Hospital — Чжэнчжоу
• … и ещё 14 центров

Идентификаторы

NCT: NCT06122831 · TQ05105-TQB3617-Ib/II-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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