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

December 19, 2023 updated by: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

78

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 525000
        • Not yet recruiting
        • Guangdong Provincial People's Hospital
        • Contact:
    • Guangxi
      • Nanning, Guangxi, China, 530016
        • Not yet recruiting
        • Guangxi Zhuang Autonomous Region People's Hospital
        • Contact:
    • Hebei
      • Cangzhou, Hebei, China, 061014
        • Not yet recruiting
        • Cangzhou People's Hosipital
        • Contact:
      • Chengde, Hebei, China, 067020
        • Not yet recruiting
        • Affiliated Hospital of Chengde Medical College
        • Contact:
      • Tangshan, Hebei, China, 063000
        • Not yet recruiting
        • North China of Science and Technology University Affiliated Hospital
        • Contact:
      • Xingtai, Hebei, China, 054031
        • Not yet recruiting
        • Xingtai People's Hospital
        • Contact:
    • Heilongjiang
      • Harbin, Heilongjiang, China, 150010
        • Not yet recruiting
        • The First Hospital of Harbin
        • Contact:
          • Tiejun Gong, Master
          • Phone Number: 13836027737
          • Email: arc@sina.con
    • Henan
      • Zhengzhou, Henan, China, 450003
        • Not yet recruiting
        • Henan Cancer Hospital
        • Contact:
    • Hubei
      • Wuhan, Hubei, China, 430071
        • Not yet recruiting
        • Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology
        • Contact:
      • Wuhan, Hubei, China, 430071
        • Not yet recruiting
        • Union Hospital Tongji College Huazhong Unizersity of Science And Technology
        • Contact:
      • Wuhan, Hubei, China, 430071
        • Not yet recruiting
        • Wuhan University Zhongnan Hospital
        • Contact:
    • Inner Mongolia
      • Hohhot, Inner Mongolia, China, 010000
        • Not yet recruiting
        • The affiliated hospital of Inner Mongolia Medical University
        • Contact:
    • Jiangsu
      • Wuxi, Jiangsu, China, 214000
        • Not yet recruiting
        • The Public Hospital of Wuxi
        • Contact:
    • Jilin
      • Changchun, Jilin, China, 130021
        • Not yet recruiting
        • The First Hospital of Jilin University
        • Contact:
    • Shaanxi
      • Xi'an, Shaanxi, China, 710000
        • Not yet recruiting
        • Xi 'An Jiaotong University Second Affiliated Hospital
        • Contact:
    • Shanghai
      • Shanghai, Shanghai, China, 200233
      • Shanghai, Shanghai, China, 200000
        • Recruiting
        • Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine
        • Contact:
    • Shanxi
      • Changzhi, Shanxi, China, 046000
        • Not yet recruiting
        • Heping Hospital Affiliated to Changzhi Medical College
        • Contact:
    • Tianjin
      • Tianjin, Tianjin, China, 300122
        • Not yet recruiting
        • People's Hospital of Tianjin City
        • Contact:
    • Xinjiang
      • Ürümqi, Xinjiang, China, 830011
        • Not yet recruiting
        • The First Affiliated Hospital of Xinjiang Medical University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.
  • Patients with poor efficacy of JAK inhibitors (for phase Ib and phase II cohort 2)
  • 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;
  • Patients who have previously undergone splenectomy, or received splenic radiotherapy within 6 months before the first administration;
  • Use of any MF medications, any immunomodulators, androgens, any immunosuppressive agents, erythropoietin, aspirin > 100 mg/day within 2 weeks prior to 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;
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TQ05105 Tablets + TQB3617 Capsules
TQ05105 Tablets combined with TQB3617 Capsules, orally administered. 21 days as a treatment cycle.
Drug: TQ05105 Tablets
TQ05105 Tablets is a Janus kinase 1 (JAK1) and Janus kinase 2 (JAK2) Inhibitor.
Drug: TQB3617 Capsules
TQB3617 Capsules is a Bromodomain and Extra-Terminal (BET) Inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximal tolerance dose (MTD)
Time Frame: 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.
Up to 2 years.
Recommended phase II dose (RP2D)
Time Frame: Up to 2 years
The RP2D is defined as the lower dose level to MTD based on the safety profile.
Up to 2 years
≥35% reduction in spleen volume (SVR35)
Time Frame: 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.
Up to 24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
SVR35
Time Frame: Up to 120 weeks
The proportion of subjects with a ≥35% reduction in spleen volume compared to baseline after treatment.
Up to 120 weeks
Optimum effective rate
Time Frame: Up to 120 weeks
The proportion of subjects with at least once spleen volume reduction ≥ 35% from baseline.
Up to 120 weeks
Onset time of splenic response
Time Frame: Up to 120 weeks
The time interval from the first administration to the date when the spleen volume was reduced by ≥ 35 % from baseline.
Up to 120 weeks
Duration of maintenance of at least 35% Reduction in Spleen Volume (DoMSR)
Time Frame: Up to 120 weeks
The time between the date when the spleen volume reduction ≥ 35% from baseline occurs for the first time and the date when the spleen volume reduction is < 35% from baseline.
Up to 120 weeks
Myeloproliferative neoplasm - Symptom Assessment Form - Total Symptom Score (MPN-SAF TSS)
Time Frame: Up to 60 weeks
The proportion of subjects whose total symptom score of MPN-SAF TSS decreased by more than 50% from baseline. MPN-SAF-TSS is an effective tool for evaluating the disease burden of patients with myeloproliferative neoplasms. Each symptom is scored according to the severity, from asymptomatic (0 points) to the most serious (10 points), a total of 10 levels, the sum of 10 symptom scores is MPN-SAF-TSS score. The higher the score, the more severe the symptoms are.
Up to 60 weeks
Variant allele frequency (VAF)
Time Frame: Up to 48 weeks
The proportion of subjects whose VAF decreased compared with baseline.
Up to 48 weeks
The proportion of subjects with gene mutation achieving SVR35
Time Frame: Up to 48 weeks
The proportion of subjects with gene mutation achieving SVR35
Up to 48 weeks
The proportion of subjects with gene mutation whose MPN-SAF TSS scale decreased by ≥ 50%
Time Frame: Up to 48 weeks.
The proportion of subjects with gene mutation whose MPN-SAF TSS scale decreased by ≥ 50% compared with baseline.
Up to 48 weeks.
Progression-free survival (PFS)
Time Frame: Up to 120 weeks
The time interval from the first dose 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
Leukemia free survival (LFS)
Time Frame: Up to 120 weeks
The time interval from the date of the first dose to the date of any of the following events, whichever occurs first: (1) the date of the first bone marrow smear showing the original cell ≥20% ;(2) The first peripheral blood smear showed that the original cells ≥ 20% and the absolute value of the original cells ≥1×10^9/L and lasted for at least 2 weeks; (3) Death caused by any reason.
Up to 120 weeks
Overall Survival (OS)
Time Frame: Up to 120 weeks
OS is defined as the time from the first time the subject received treatment to death due to any cause.
Up to 120 weeks
Incidence of adverse events (AEs)
Time Frame: Baseline up to 120 weeks
Incidence rate of all adverse medical events that occur after the subject receives the investigational drug, evaluated according to the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0)
Baseline up to 120 weeks
Severity of adverse events (AEs)
Time Frame: Baseline up to 120 weeks
Severity of all adverse medical events that occur after the subject receives the investigational drug, evaluated according to the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0)
Baseline up to 120 weeks
MPN-SAF TSS change
Time Frame: Up to 120 weeks
The total score of MPN-SAF TSS decreased compared with baseline. MPN-SAF-TSS is an effective tool for evaluating the disease burden of patients with myeloproliferative neoplasms. Each symptom is scored according to the severity, from asymptomatic (0 points) to the most serious (10 points), a total of 10 levels, the sum of 10 symptom scores is MPN-SAF-TSS score. The higher the score, the more severe the symptoms are.
Up to 120 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 12, 2023

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

April 1, 2027

Study Registration Dates

First Submitted

November 2, 2023

First Submitted That Met QC Criteria

November 3, 2023

First Posted (Actual)

November 8, 2023

Study Record Updates

Last Update Posted (Estimated)

December 21, 2023

Last Update Submitted That Met QC Criteria

December 19, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TQ05105-TQB3617-Ib/II-01

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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