Diffuse Large B-cell Lymphoma (DLBCL), High-grade B-cell Lymphoma (HGBL), Primary Mediastinal Large B-cell Lymphoma (PMBCL), Refractory Large B-cell Lymphoma, Relapsed Large B-cell Lymphoma, Transformed Follicular Lymphoma (TFL)
Conditions
Keywords
TC011, CAR-T, Chimeric antigen receptor, CLIP
Brief summary
This is a multi-center, phase I/II study to determine the safety and efficacy of TC011(CD19 Targeted CAR-T) in adult patients with relapsed or refractory large B-cell non -hodgkin lymphoma.
Interventions
DRUGTC011
Anti-CD19 Chimeric Antigen Receptor T cell
Sponsors
TICAROS Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subjects must meet all criteria including: * ≥19 years old, ECOG 0-2, life expectancy ≥12 weeks * Histologically confirmed B-cell lymphoma (WHO 2017) * Relapsed/refractory after ≥2 prior lines of systemic chemotherapy * ≥1 measurable lesion (longest diameter ≥1.5 cm) * Adequate organ, and pulmonary function * LVEF ≥40% * Able to undergo leukapheresis * For subjects of childbearing potential: agreement to use effective contraception for ≥6 months after TC011 infusion
Exclusion criteria
* Unresolved ≥Grade 2 toxicities from prior therapy * Malignancy within 2 years except specified exceptions * Significant cardiac disease within 6 months * CNS involvement by lymphoma * Active HBV, HCV, HIV, syphilis * Rapidly progressing disease per investigator * Major surgery requiring general anesthesia within 4 weeks * Active or uncontrolled infection * Prior therapies such as anti-CD19 agents, adoptive T-cell therapy, gene therapy, allogeneic HSCT * Use of other investigational agents, immunosuppressants within protocol-specified windows * Pregnancy or breastfeeding * Hypersensitivity to study drug components * Leukapheresis-specific exclusions (recent chemotherapy, steroids, immunosuppressants)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase1: Occurrence of Dose-Limiting Toxicities (DLTs) | Up to 4 weeks after TC011 infusion | A dose-limiting toxicity (DLT) is defined as any toxicity that is definitely related or probably related to the administration of TC011. The severity of toxicities will be assessed according to CTCAE Version 5.0, while cytokine-release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) will be evaluated based on the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading . |
| Phase1: Determination of Maximum Tolerated Dose (MTD) | up to 4weeks after TC011 infusion | DLT occurrence within the first 4 weeks after treatment initiation will be used to determine the maximum tolerated dose (MTD) . |
| Phase1: Determination of Recommended Phase 2 Dose (RP2D) | Up to 12 weeks after TC011 infusion | The recommended Phase 2 dose (RP2D) will be determined based on evaluation of safety (including DLT incidence), tolerability, overall adverse event profile, and preliminary anti-tumor activity observed during the dose-escalation phase. |
| Phase 1: The number and incidence rate of treatment-emergent adverse events (TEAEs) as well as serious adverse events (SAEs) will be assessed | Up to 12 weeks after TC011 infusion | All adverse events (AEs) will be graded according to CTCAE version 5.0. Adverse events of special interest include cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which will be graded according to American Society for Transplantation and Cellular Therapy (ASTCT) consensus criteria. |
| Phase1: Number of participants with abnormal physical examination findings | Baseline through Week 12 | Clinically significant abnormalities identified during comprehensive physical examinations (general appearance, cardiovascular, respiratory, abdominal, neurologic, lymphatic systems) will be recorded. |
| Phase1: Number of participants with abnormal vital signs | Baseline through Week 12 | Abnormal vital signs (systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate, and body temperature) will be documented according to clinical significance. |
| Phase1: Number of participants with abnormal ECG readings | Baseline through Week 12 | ECG findings will be categorized as Normal, Abnormal - Not Clinically Significant, or Abnormal - Clinically Significant. |
| Phase 1 : Number of participants with abnormal laboratory test results | Baseline through Week 12 | Abnormal results from hematology, chemistry, liver function tests, renal function tests, coagulation, and other relevant laboratory parameters will be recorded. |
| Phase 1 : Presence of Replication-Competent Lentivirus (RCL) Through Week 12 | Baseline through Week 12 | Peripheral blood samples will be collected to evaluate the presence of replication-competent lentivirus (RCL). Samples will be analyzed by the central laboratory (BioComplete). If RCL is detected by quantitative PCR, additional confirmatory analyses and patient follow-up- including assessment of medical history for lentivirus-associated diseases such as malignancies, neurological disorders, or serologic conditions-will be conducted. |
| Phase 2 : Objective Response Rate (ORR) | up to 24 weeks after TC011 infusion | as the proportion of subjects achieving complete response (CR) or partial response (PR) as their best overall response (BOR) per the Lugano Criteria for Response Assessment (2014). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Overall response rate (ORR) | 4weeks and 12weeks after TC011 infusion | To explore the efficacy of the TC011, evaluate tumor response 4weeks and 12weeks after TC011 administration according to 2014 Lugano classification |
| Phase 2: Objective response rate (ORR) | Weeks 4, 12, 24, 48, 72, and 96 | — |
| Phase 2 Disease control rate (DCR) | at Weeks 4, 12, 24, 48, 72, and 96 | — |
| Phase 2: Complete response rate (CRR) | at Weeks 4, 12, 24, 48, 72, and 96 | — |
| Phase 2: Partial response rate (PRR) | at Weeks 4, 12, 24, 48, 72, and 96 | — |
| Phase 2: Stable disease rate (SDR) | at Weeks 4, 12, 24, 48, 72, and 96 | — |
| Phase 2: Progression-free survival (PFS) | at Weeks 4, 12, 24, 48, 72, and 96 | — |
| Phase 2: Overall survival (OS) | at Weeks 4, 12, 24, 48, 72, and 96 | — |
| Phase 2: Time to response (TTR) | at Weeks 4, 12, 24, 48, 72, and 96 | — |
Countries
South Korea
Contacts
CONTACTAh hyun Lim
CONTACTadmin
Outcome results
None listed