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

July 18, 2024 updated by: Rong Tao, Fudan University
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

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
9

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

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:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Rate of dose-limiting toxicities (DLTs)
Time Frame: 28 days
Dose limiting toxicities for each subject
28 days
AE/SAE
Time Frame: 24 months
Incidence and severity of adverse events (AE), and serious adverse event (SAE)
24 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Copy number of the vector transgene of JWCAR201 in peripheral blood
Time Frame: 24 months
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
Time Frame: 24 months
CD19-positive cells and CD20-positive cells in peripheral blood will be tested by flow cytometry (FCM).
24 months
Objective response rate (ORR)
Time Frame: 24 months
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)
Time Frame: 24 months
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)
Time Frame: 24 months
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)
Time Frame: 24 months
The time from JWCAR201 infusion to the date of progression as assessed by Lugano criteria or death.
24 months
Overall survival (OS)
Time Frame: 24 months
Defined as the time from the date of first infusion of JWCAR201 to death due to any cause.
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fudan University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Rong Tao, MD, Fudan University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 18, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 18, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 18, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 24, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 24, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 18, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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