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 Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
92
TQ05105 Tablets is a Janus kinase 1 (JAK1) and Janus kinase 2 (JAK2) Inhibitor.
TQB3617 Capsules is a Bromodomain and Extra-Terminal (BET) Inhibitor
Maximal tolerance dose (MTD)
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.
Time frame: Up to 2 years.
Recommended phase II dose (RP2D)
The RP2D is defined as the lower dose level to MTD based on the safety profile.
Time frame: Up to 2 years
≥35% reduction in spleen volume (SVR35)
The proportion of subjects with a ≥35% reduction in spleen volume from baseline at the end of treatment at week 24.
Time frame: Up to 24 weeks
SVR35
The proportion of subjects with a ≥35% reduction in spleen volume compared to baseline after treatment.
Time frame: Up to 120 weeks
Optimum effective rate
The proportion of subjects with at least once spleen volume reduction ≥ 35% from baseline.
Time frame: Up to 120 weeks
Onset time of splenic response
The time interval from the first administration to the date when the spleen volume was reduced by ≥ 35 % from baseline.
Time frame: Up to 120 weeks
Duration of maintenance of at least 35% Reduction in Spleen Volume (DoMSR)
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.
Time frame: Up to 120 weeks
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Guangdong Provincial People's Hospital
Guangzhou, Guangdong, China
NOT_YET_RECRUITINGGuangxi Zhuang Autonomous Region People's Hospital
Nanning, Guangxi, China
NOT_YET_RECRUITINGCangzhou People's Hosipital
Cangzhou, Hebei, China
NOT_YET_RECRUITINGAffiliated Hospital of Chengde Medical College
Chengde, Hebei, China
NOT_YET_RECRUITINGNorth China of Science and Technology University Affiliated Hospital
Tangshan, Hebei, China
NOT_YET_RECRUITINGXingtai People's Hospital
Xingtai, Hebei, China
NOT_YET_RECRUITINGThe First Hospital of Harbin
Harbin, Heilongjiang, China
NOT_YET_RECRUITINGHenan Cancer Hospital
Zhengzhou, Henan, China
NOT_YET_RECRUITINGTongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology
Wuhan, Hubei, China
NOT_YET_RECRUITINGUnion Hospital Tongji College Huazhong Unizersity of Science And Technology
Wuhan, Hubei, China
NOT_YET_RECRUITING...and 12 more locations
Myeloproliferative neoplasm - Symptom Assessment Form - Total Symptom Score (MPN-SAF TSS)
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.
Time frame: Up to 60 weeks
MPN-SAF TSS change
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.
Time frame: Up to 120 weeks
Variant allele frequency (VAF)
The proportion of subjects whose VAF decreased compared with baseline.
Time frame: Up to 48 weeks
The proportion of subjects with gene mutation achieving SVR35
The proportion of subjects with gene mutation achieving SVR35
Time frame: Up to 48 weeks
The proportion of subjects with gene mutation whose MPN-SAF TSS scale decreased by ≥ 50%
The proportion of subjects with gene mutation whose MPN-SAF TSS scale decreased by ≥ 50% compared with baseline.
Time frame: Up to 48 weeks.
Progression-free survival (PFS)
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.
Time frame: Up to 120 weeks
Leukemia free survival (LFS)
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.
Time frame: Up to 120 weeks
Overall Survival (OS)
OS is defined as the time from the first time the subject received treatment to death due to any cause.
Time frame: Up to 120 weeks
Incidence of adverse events (AEs)
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)
Time frame: Baseline up to 120 weeks
Severity of adverse events (AEs)
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)
Time frame: Baseline up to 120 weeks