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(Limit: 5000 characters) The purpose of this phase I clinical study aims to evaluate the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of SYS6055 Injection in participants with relapsed/refractory B-cell malignancies, and to provide evidence for recommending a dosage regimen for subsequent studies.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose Escalation and Backfill | Experimental | In the dose escalation phase, participants will receive escalating doses of SYS6055. During the backfill phase, participants will receive selected doses of SYS6055. Participants will be administered a single dose on Day 0 of Cycle 1. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SYS6055 | Drug | The dose will be selected based on the dose cohort, with a single administration. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Dose-limiting toxicities (DLTs) | Dose-limiting toxicities (DLTs) will be assessed 28 days after the first dose. | |
| Occurrence of Adverse Events (AE) and Serious Adverse Events (SAE) | Up to 24 months after administration of 6055 | |
| Recommended Phase 2 Dose (RP2D) or Maximum Tolerated Dose (MTD) of SYS6055 | through study completion, an average of 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate (ORR) | through study completion, an average of 3 years | |
| Time to Response(TTR) | through study completion, an average of 3 years | |
| Duration of Response (DoR) |
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Inclusion Criteria:
Exclusion Criteria:
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| ID | Term |
|---|---|
| D012008 | Recurrence |
| ID | Term |
|---|---|
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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This is an open-label, single-arm, dose-escalation study using an accelerated titration design combined with a traditional 3+3 design. Six dose cohorts are enrolled, and dose-limiting toxicities (DLTs) are assessed after dosing in Cycle 1 (28 days). The Safety Monitoring Committee (SMC) continuously reviews and monitors the safety of the investigational product.
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| through study completion, an average of 3 years |
| Progression-free survival (PFS) | through study completion, an average of 3 years |
| Overall Survival (OS) | through study completion, an average of 3 years |
| PK, CD19-CAR copy number and CD19 CAR-T cell content of SYS6055 | The levels of CD19 CAR RNA and DNA in peripheral blood will be determined by qPCR, with the proportion of CD19 CAR-T cells assessed by flow cytometry. | 2 years |
| PK, CD19 CAR-T cell phenotypes | CD19 CAR-T cell phenotypes will be analyzed by flow cytometry, including CD4/CD8 ratio, naïve cells, memory cells, and effector cells. | 2 years |
| PD | Levels of cytokines in peripheral blood (IL-6, IL-10, IFN-γ, TNF-α, etc.). | 2 years |
| PD | CRP | 2 years |
| PD | ferritin levels | 2 years |
| PD | immunoglobulin levels (IgG, IgA, IgM) | 2 years |
| PD | peripheral blood lymphocyte subsets (proportion and absolute counts of T, B, and NK cells),Lymphocyte subsets will be analyzed by flow cytometry. | 2 years |
| Immunogenicity | Incidence of anti-CD19-CAR antibodies and antiviral antibodies. | 2 years |
| Viral shedding | Peripheral blood, urine, saliva, and fecal samples will be collected at predefined time points for the assessment of viral shedding. | 2 years |
| Replication-competent virus detection | Peripheral blood, urine, saliva, and fecal samples will be collected at predefined time points for the assessment of viral shedding. | 2 years |
| Viral integration site analysis | Peripheral blood, urine, saliva, and fecal samples will be collected at predefined time points for the assessment of viral shedding. | 2 years |