An Open-label, Single-arm Study of JWCAR201 in the Treatment of Relapsed or Refractory Diffuse Large B-cell Lymphoma

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).

Study Overview

• Status: Recruiting
• Conditions: Diffuse Large B Cell Lymphoma
• Intervention / Treatment: Biological: JWCAR201

Detailed Description

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
• Enrollment (Estimated): 9
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Rong Tao, MD; Phone Number: +8621-64175590; Email: rtao@shca.org.cn
• Study Contact Backup: Name: Wenhao Zhang, MD; Phone Number: +8621-64175590

Study Locations

• China
  • Shanghai, China, 200032
    • Recruiting
    • Fudan University Shanghai Cancer Center
    • Principal Investigator: Rong Tao, MD
    • Contact: Rong Tao, MD; Phone Number: 8621-64175590; Email: rtao@shca.org.cn
    • Contact: Chuanxu Liu, MD; Phone Number: 8621-64175590; Email: liuchuanxu@shca.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18
2. Voluntarily willing to participate in the study and sign the written informed consent form
3. Histologically confirmed diffuse large B-cell lymphoma (DLBCL) with immunohistochemistry (IHC) CD20-positive
4. Patients must be priorly treated by Anthracyclines and anti-CD20-targeted regimens, and must be refractory or relapsed to at least ≥2 treatment lines of standard of care or autologous hematopoietic stem-cell transplantation (HSCT)
5. At least one measurable lesion by CT or PET per Lugano criteria
6. Eastern Cooperative Oncology Group (ECOG) performance status scale ≤1
7. Adequate organ functions
8. Adequate venous access for apheresis
9. Women of childbearing potential must agree to use an effective and reliable contraceptive method till 1-year post-infusion
10. Male patients who have not undergone vasectomy and have sexual activity with women of childbearing potential must agree to the use of a barrier contraceptive till 1-year post-infusion

Exclusion Criteria:

1. Primary central nervous system lymphoma
2. Another primary malignancy within 2 years
3. Active infections of hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), or syphilis
4. With severe active deep venous thrombosis or pulmonary embolism within 3 months
5. Treated with anti-coagulations (except for prophylaxis use) due to severe active deep venous thrombosis or pulmonary embolism within 3 months
6. Uncontrolled or active infection
7. Acute or chronic graft-versus-host disease (GvHD)
8. With severe cardiovascular diseases within 6 months
9. With severe clinically-significant central nervous system disorders within 6 months
10. Pregnant or lactating women
11. Not satisfying pre-defined wash-out period for apheresis
12. Unable or unwilling to comply with the study protocol, judged by the investigator, or other situations implying that the subject might not be appropriate to participate in the study
13. Previously treated with any genetically engineered modified T-cell therapy nor other cell-gene therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JWCAR201 Treatment Arm; Patients will be administrated with autologous CD19/CD20-directed CAR-T cells after lymphocyte depletion by fludarabine and cyclophosphamide.	Biological: JWCAR201; Autologous CD19/CD20-directed CAR-T cells, single infusion intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of dose-limiting toxicities (DLTs)	Dose limiting toxicities for each subject	28 days
AE/SAE	Incidence and severity of adverse events (AE), and serious adverse event (SAE)	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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).	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.	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.	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.	24 months
Progression-free survival (PFS)	The time from JWCAR201 infusion to the date of progression as assessed by Lugano criteria or death.	24 months
Overall survival (OS)	Defined as the time from the date of first infusion of JWCAR201 to death due to any cause.	24 months

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Rong Tao, MD, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: July 18, 2024
• First Submitted That Met QC Criteria: July 18, 2024
• First Posted (Actual): July 24, 2024

Study Record Updates

• Last Update Posted (Actual): July 24, 2024
• Last Update Submitted That Met QC Criteria: July 18, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Diffuse Large B Cell Lymphoma; CAR-T therapy
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse
• Other Study ID Numbers: JWCAR201002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No