Relmacabtagene Autoleucel as First-Line Therapy for High-Risk Large B-Cell Lymphoma

January 5, 2024 updated by: Peking University Cancer Hospital & Institute

Study to Evaluate the Efficacy and Safety of Relmacabtagene Autoleucel (Relma-cel) as First-Line Therapy in Adult Participants With High-Risk Large B-Cell Lymphoma

The primary objective of this study is to estimate the efficacy of Relmacabtagene Autoleucel in participants with high-risk large B-cell lymphoma.

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 a prospective, open-label, multicenter, single-arm trial, assessed the efficacy and safety of JWCAR029(relma-cel) as part of first-line therapy after an incomplete first-line treatment regimen of two cycles of chemoimmunotherapy. High-risk LBCL was defined by the dynamic risk assessment of interim PET2+, together with either double- or triple-hit lymphomas or high-intermediate- and high-risk IPI scores (≥3). All sujects will be followed for 2 years following JWCAR029 infusion.

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.
20

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 2

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

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100010
        • Recruiting
        • Beijing Cancer Hospital
        • Contact:
          • Yuqin Song, PhD
      • Beijing, Beijing, China, 100010
        • Recruiting
        • Peking University International Hospital
        • Contact:
          • Liu xinjian
    • Henan
      • Zhengzhou, Henan, China, 450003
    • Tianjin
      • Tianjin, Tianjin, China, 300060
        • Not yet recruiting
        • Tianjin Medical University Cancer Institute and Hospital
        • 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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. ≥ 18 years old;
  2. Sign on the informed consent;
  3. Histologically confirmed large B-cell lymphoma that also meets the definition of high-risk large B-cell lymphoma as a lymphoma International Prognostic Index (IPI) score of 3-5 and/or high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangement (double/triple-hit lymphoma) (DHL/THL) and must be treated with 2 cycles of CD20 monoclonal antibodies combined with anthracyclines. Presence of positive PET assessable lesions (DS score of 4 or 5) as determined by the Lugano criteria (Cheson et al., 2014)；
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
  5. Expected survival greater than 12 weeks；

  6. Adequate organ function：

    1. Absolute neutrophil count ≥ 1000/μL；Absolute lymphocyte count ≥ 100/μL； Platelet count ≥ 75,000/μL；Hb ≥ 80g/L；
    2. Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or creatinine clearance (Cockcroft-Gault formula) > 50 mL/min (serum creatinine clearance due to lymphoma mass compression should be > 30 mL/min)；
    3. Serum alanine aminotransferase (ALT) ≤ 5 upper limit of normal (ULN) and total bilirubin ≤2ULN（or for subjects with Gilbert's syndrome or lymphoma invading the liver < 3 ULN）；
    4. Baseline oxygen saturation > 92% on room air；
    5. Left ventricular ejection fraction (LVEF) ≥50% assessed by echocardiography or radionuclide activity angiography (MUGA) within 1 month of enrollment；
  7. Adequate vascular access for leukapheresis procedure;
  8. Women of childbearing potential must agree to use highly effective methods of contraception for at least 28 days prior to lymphocyte clearance chemotherapy through 1 year after Relmacabtagene Autoleucel infusion; Males who have partners of childbearing potential must agree to use an effective barrier contraceptive method for 1 year after Relmacabtagene Autoleucel infusion.

Exclusion Criteria:

  1. Lymphoma involving the central nervous system (CNS)；
  2. History of another primary malignancy that has not been in remission for at least 2 years;
  3. History of Richter's transformation of chronic lymphocytic leukemia or primary mediastinal B-cell lymphoma；
  4. Subjects has HBV, HCV, HIV or syphilis infection at the time of screening;
  5. Deep venous thrombosis (DVT)/Pulmonary embolism (PE), or DVT/PE requires anti-coagulation within 3 months prior to signing the ICF;
  6. Subjects with uncontrolled systemic fungal, bacterial, viral or other infection;
  7. Presence of acute or chronic graft-versus-host disease (GVHD);
  8. History of any serious cardiovascular disease or presence of clinically relevant CNS pathology;
  9. Pregnant or nursing women;
  10. Subjects Received an autologous or allogeneic hematopoietic stem cell transplant；
  11. Uncontrolled conditions or unwillingness or inability to follow the procedures required in the protocol;
  12. Received CAR T-cell or other genetically-modified T-cell therapy previously；
  13. Received live vaccination within 6 weeks prior to lymphocyte clearance chemotherapy；
  14. History of severe hypersensitivity reactions to any of the drug ingredients used in this study product.

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: Relmacabtagene Autoleucel
Participants will receive cyclophosphamide250 mg/m^2/day intravenously (IV) and fludarabine 25 mg/m^2/day IV conditioning chemotherapy for 3 days followed by Relmacabtagene Autoleucel administered as a single IV infusion at a target dose of 1 x 10^8 anti-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) transduced autologous T cells on Day 1.
Drug: Cyclophosphamide
Administered according to package insert
Drug: Fludarabine
Administered according to package insert
Biological: Relmacabtagene Autoleucel
A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells
Other Names:
  • JWCAR029

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
Complete Response (CR) Rate Per the Lugano Classification as Determined by Study Investigators
Time Frame: up to 2 years after Relmacabtagene Autoleucel infusion
Complete Response Rate (CRR): percentage of participants with CR [complete metabolic response (CMR); complete radiological response (CRR)]. CMR: positron emission tomography (PET) 5-point scale (5-PS) scores of 1 (no uptake above background), 2 (uptake ≤ mediastinum), 3 (uptake > mediastinum but ≤ liver) with/without a residual mass); no new lesions; and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow (BM). CRR: target nodes/nodal masses regressed to ≤ 1.5 cm in longest transverse diameter of lesion (LDi); no extralymphatic sites of disease; absent non-measured lesion (NMLs); organ enlargement regress to normal; no new sites; and bone marrow normal by morphology.
up to 2 years after Relmacabtagene Autoleucel infusion

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
Objective Response Rate (ORR) Per the Lugano Classification as Determined by Study Investigators
Time Frame: up to 2 years after Relmacabtagene Autoleucel infusion
ORR: percentage of participants with CR [CMR;CRR] or PR [partial metabolic response (PMR); partial radiologic response (PRR)].CMR: PET 5PS scores of 1 (no uptake above background, 2 (uptake ≤ mediastinum), 3 (uptake > mediastinum but ≤ liver) with/without a residual mass; no new lesions; no evidence of FDG-avid disease in BM. CRR:target nodes/nodal masses regressed to ≤ 1.5 cm in LDi;no extralymphatic sites of disease;absent NMLs;organ enlargement regress to normal;no new sites;bone marrow morphology normal. PMR:scores 4 (uptake moderately > liver),5 (uptake markedly > liver, new lesions) with reduced uptake compared with baseline and residual mass;no new lesions;responding disease at interim/residual disease at end of treatment (EOT).PRR: ≥ 50% decrease in sum of the product of perpendicular diameters (SPD) of up to 6 target measurable nodes and extra-nodal sites;absent/normal, regressed, but no increase of NMLs;spleen regressed by > 50% in length beyond normal;no new sites.
up to 2 years after Relmacabtagene Autoleucel infusion
Duration of Response (DOR) Per the Lugano Classification
Time Frame: up to 2 years after Relmacabtagene Autoleucel infusion
DOR is defined only for participants who experience an objective response after Relmacabtagene Autoleucel infusion and is the time from the first objective response to disease progression or death from any cause. Objective response is defined in outcome measure (OM) 2.
up to 2 years after Relmacabtagene Autoleucel infusion
Event-Free Survival (EFS)
Time Frame: up to 2 years after Relmacabtagene Autoleucel infusion
First infusion date of Relmacabtagene Autoleucel to data cut off
up to 2 years after Relmacabtagene Autoleucel infusion
Progression-Free Survival (PFS)
Time Frame: up to 2 years after Relmacabtagene Autoleucel infusion
PFS is defined as the time from the Relmacabtagene Autoleucel infusion date to the date of disease progression per Lugano classification or death from any cause.
up to 2 years after Relmacabtagene Autoleucel infusion
Overall Survival (OS)
Time Frame: up to 2 years after Relmacabtagene Autoleucel infusion
OS is defined as the time from Relmacabtagene Autoleucel infusion to the date of death from any cause.
up to 2 years after Relmacabtagene Autoleucel infusion
Types, frequency, and severity of adverse events and laboratory anomalies
Time Frame: up to 2 years after Relmacabtagene Autoleucel infusion
Physiological parameter
up to 2 years after Relmacabtagene Autoleucel infusion
Pharmacokinetic (PK)- Cmax of Relmacabtagene Autoleucel
Time Frame: up to 1 year after Relmacabtagene Autoleucel infusion
Maximum observed concentration of Relmacabtagene Autoleucel in peripheral blood
up to 1 year after Relmacabtagene Autoleucel infusion
Pharmacokinetic (PK)- Tmax of Relmacabtagene Autoleucel
Time Frame: up to 1 year after Relmacabtagene Autoleucel infusion
Time to maximum concentration of Relmacabtagene Autoleucel in peripheral blood
up to 1 year after Relmacabtagene Autoleucel infusion
Pharmacokinetic (PK)- AUC of Relmacabtagene Autoleucel
Time Frame: up to 1 year after Relmacabtagene Autoleucel infusion
Area under the concentration vs time curve of Relmacabtagene Autoleucel
up to 1 year after Relmacabtagene Autoleucel infusion
The concentration of Car-T cell
Time Frame: up to 1 year after Relmacabtagene Autoleucel infusion
The concentration of Car-T cell in peripheral blood
up to 1 year after Relmacabtagene Autoleucel infusion
The change of serum cytokines concentration
Time Frame: up to 1 year after Relmacabtagene Autoleucel infusion
The change of serum cytokines(IL-2、IL-4、IL-6、IL-8、IL-10、IL-17A、IFN-γ、TNF-α、IFN-α) concentration after Relmacabtagene Autoleucel infusion
up to 1 year after Relmacabtagene Autoleucel infusion

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.
Peking University Cancer Hospital & Institute

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Shanghai Ming Ju Biotechnology Co., Ltd.

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: Yuqin Song, PhD, Peking University Cancer Hospital & Institute

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.
January 3, 2023

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.
February 10, 2024

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.
December 10, 2024

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).
October 12, 2022

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.
October 19, 2022

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.
October 21, 2022

Study Record Updates

Last Update Posted (Estimated)

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.
January 8, 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.
January 5, 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.
November 1, 2023

More Information

Terms related to this study

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.
  • JWCAR029011

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

product manufactured in and exported from the U.S.

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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