This is an open-label, single-arm study to investigate the efficacy and safety signals of JWCAR201 amongst subjects with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
This is an open-label, single-arm, investigator-initiated study (IIT) to evaluate the safety an JWCAR201 in adult patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). The study employs a two-stage, Continual Reassessment Method (CRM)-like dose escalation design. In the first stage, each dose cohort will use an accelerated titration approach, escalating to the dose level at which a Dose-Limiting Toxicity (DLT) occurs or the 50 × 10\^6 CAR+ T-cell dose level (whichever is reached first). The second stage will start at observed DLT dose level or the 50\^6 CAR+ T-cell dose level, an model-based CRM method using a single-parameter Logistic model will be used to describe the relationship between the JWCAR201 dose and the probability of observed DLTs. The Maximum Tolerated Dose (MTD) is defined as the highest an estimated DLT probability below the 25% target toxicity level. For each dose level, a prior mean DLT risk (skeleton) will be set based on historical data. After enrolling ≥3 patients perort, the prior DLT risk will be updated based on the available study data, and the DLT risk will be communicated to the Data Safety Monitoring Committee to recommend the next cohort dose. The study plans to start at 25 × 10\^6 CAR+ T cells as the initial dose, with exploration across three dose levels (25 × 10\^6, 50 × 10\^6, 75 × 10\^6 CAR+ T cells), and 15 × 10\^6 CAR+ T cells or lower and 100 × 10\^6 CAR+ T cells or higher as backup doses, aiming to evaluate the safety, tolerability of JWCAR201 in r/r DLBCL and determine the recommended dose for expansion. Additionally, pharmacokinetic and pharmacodynamic characteristics are also study objectives.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
Autologous CD19/CD20-directed CAR-T cells, single infusion intravenously
Fudan University Shanghai Cancer Center
Shanghai, China
RECRUITINGRate of dose-limiting toxicities (DLTs)
Dose limiting toxicities for each subject
Time frame: 28 days
AE/SAE
Incidence and severity of adverse events (AE), and serious adverse event (SAE)
Time frame: 24 months
Copy number of the vector transgene of JWCAR201 in peripheral blood
The pharmacokinetic parameters of JWCAR201 will be evaluated by quantitative polymerase chain reaction (qPCR) for the copy number of the vector transgene of JWCAR201 in peripheral blood to evaluate T-cell expansion and persistence.
Time frame: 24 months
CD19-positive cells and CD20-positive cells in peripheral blood
CD19-positive cells and CD20-positive cells in peripheral blood will be tested by flow cytometry (FCM).
Time frame: 24 months
Objective response rate (ORR)
Proportion of patients whose tumor volume has reached a predetermined value and can maintain a minimum time limit, including complete response and partial response patients.
Time frame: 24 months
Complete response rate (CRR)
The percentage of patients with advanced or metastatic cancer who have achieved complete response to a therapeutic intervention in clinical trials of anticancer agents.
Time frame: 24 months
Duration of response (DOR)
The time from the date of first response (PR or better) to the date of disease progression or death after JWCAR201 infusion.
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Time frame: 24 months
Progression-free survival (PFS)
The time from JWCAR201 infusion to the date of progression as assessed by Lugano criteria or death.
Time frame: 24 months
Overall survival (OS)
Defined as the time from the date of first infusion of JWCAR201 to death due to any cause.
Time frame: 24 months