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This is an open, multi-cohort clinical study. The first phase is a dose escalation study and the second phase is a dose expansion study based on the Maximum tolerated dose (MTD) / Recommended Phase II Dose (RP2D) obtained in the first phase. The purpose is to evaluate the safety and preliminary efficacy of TQB3909 tablets combined with TQB3702 tablets in hematologic malignancy subjects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TQB3909 tablets+ TQB3702 tablets | Experimental | TQB3909 tablets combined with TQB3702 tablets, administered orally, 28 days as a treatment cycle. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TQB3909 tablets | Drug | TQB3909 is a protein inhibitor. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Dose limited toxicity (DLT) | DLT will be defined as toxicities that meet pre-defined severity criteria (according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0), and assessed as having a suspected relationship to study drug. | Baseline up to 104 weeks |
| Adverse events (AE) | The occurrence of all adverse events (AE). | Baseline up to 104 weeks |
| Serious adverse events (SAE) | The occurrence of all serious adverse events (SAE). | Baseline up to 104 weeks |
| Clinical laboratory abnormalities | Incidence of participants with abnormal clinical laboratory test results. | Baseline up to 104 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Complete remission rate (CRR)/ Complete remission with incomplete bone marrow recovery rate (CRi) | The proportion of patients with tumor hat have a complete response or complete remission with incomplete bone marrow recovery after treatment. | Baseline up to 104 weeks |
| Objective Response Rate (ORR) |
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Inclusion Criteria:
Subjects voluntarily joined the study, signed informed consent form, and with good compliance.
≥ 18 years old, ≤75 years old (when signing informed consent form); Eastern Cooperative Oncology Group (ECOG) physical status: 0-2; at least 3 months expected survival period.
Subject population:
At least 1 lesion / measurable disease for efficacy evaluation.
The function of main organs is normal.
Female patients of childbearing age should agree to use contraceptive measures during the study period and for at least 6 months after the completion of the study; a negative serum pregnancy test within 7 days prior to study enrollment and must be non-lactating subjects; male patients should agree to use contraception during the study period and for at least 6 months after the completion of the study.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yanyan Liu, Doctor | Contact | +86-13838176375 | yyliu@zzu.edu.cn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Henan Cancer Hospital | Zhengzhou | Henan | 450008 | China |
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| ID | Term |
|---|---|
| D019337 | Hematologic Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| TQB3702 tablets |
| Drug |
TQB3702 is a kinase inhibitor. |
|
The proportion of patients with tumor size reduction of a predefined amount and for a minimum time period. |
| Baseline up to 104 weeks |
| Undetectable measurable residual disease (U-MRD) ratio of peripheral blood and/or bone marrow | Refers to the undetected residual lesions. Flow cytometry was used to detect less than 1 Chronic Lymphocytic Leukemia (CLL) cell (less than 10-4) in 10,000 white blood cells in peripheral blood and/or bone marrow. | Baseline up to 104 weeks |
| Duration of complete remission / complete remission with incomplete bone marrow recovery | The time from the date of first achieving CR or CRi to the date of first definite disease progression or death from any cause (whichever occurs first). | Baseline up to 104 weeks |
| Duration of Response (DOR) | For all subjects whose best response was partial response (PR), Complete Response (CR), the time from the date of first achieving PR, CR to the date of first definite disease progression or death from any cause (whichever occurs first). | Baseline up to 104 weeks |
| Time to complete remission | The time from beginning the treatment to the first achieving complete remission/ complete remission with incomplete bone marrow recovery. | Baseline up to 104 weeks |
| Time to remission (TTR) | Time from the beginning of treatment to the first recording of remission (PR or better remission), only the remission population will be analyzed. | Baseline up to 104 weeks |
| Progression Free Survival (PFS) | The time from the first dose to the first documentation of progressive disease (PD) or death from any cause, whichever occurs first | Baseline up to 104 weeks |
| Overall Survival (OS) | The time from start of study treatment to date of death due to any cause. | Baseline up to 104 weeks |
| 2 years' PFS rate | The proportion of patients with progression free survival in 2 years. | Baseline up to 104 weeks |
| 2 years' OS rate | The proportion of patients achieving overall survival in two years. | Baseline up to 104 weeks |
| Time to reach the maximum plasma concentration (Tmax) | Time to reach the maximum plasma concentration after dose | Before the first dose of TQB3702 tablet and target dose of TQB3909 tablet. 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24 hours after the first target dose of TQB3909 tablet. The 4th /11th day before dosing with target dose of TQB3909 tablet. |
| Maximum (peak) steady-state plasma drug concentration during a dosage interval (Cmax,ss) | Cmax is the maximum plasma concentration of TQB3909 and TQB3702 | Before the first dose of TQB3702 tablet and target dose of TQB3909 tablet. 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24 hours after the first target dose of TQB3909 tablet. The 4th /11th day before dosing with target dose of TQB3909 tablet. |
| Minimum steady-state plasma drug concentration during a dosage interval (Css-min) | Cmin is the minimum plasma concentration of TQB3909 and TQB3702. | Before the first dose of TQB3702 tablet and target dose of TQB3909 tablet. 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24 hours after the first target dose of TQB3909 tablet. The 4th /11th day before dosing with target dose of TQB3909 tablet. |