LCAR-M61S and LCAR-M61D in Treatment of Relapsed/Refractory Multiple Myeloma

June 27, 2024 updated by: Chen Lijuan, The First Affiliated Hospital with Nanjing Medical University

A Clinical Study to Evaluate the Safety, Tolerance and Efficacy of LCAR-M61S and LCAR-M61D Cell Preparations in Patients With Relapsed/Refractory Multiple Myeloma

A prospective, two-cohort, open-label dose-exploration and expansion study to evaluate the safety, tolerability, pharmacokinetics, and antitumor efficacy characteristics of LCAR-M61S and LCAR-M61D in patients with relapsed/refractory multiple myeloma.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This study was a prospective, two-cohort, open-label clinical study to evaluate the safety, tolerability, pharmacokinetics, and antitumor efficacy characteristics of LCAR-M61S and LCAR-M61D in patients with relapsed/refractory multiple myeloma. All subjects who meet the eligibility criteria will receive intravenous injection of LCAR-M61S or LCAR-M61D cell injection. The study will include the following sequential phases: screening, apheresis, pre-treatment (lymphodepleting chemotherapy), treatment, and follow-up.

Study Type

Interventional

Enrollment (Estimated)

66

Phase

  • Not Applicable

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 Backup

Study Locations

  • China
    • Anhui
      • Hefei, Anhui, China, 230031
        • Anhui Cancer Hospital
        • Contact:
    • Henan
      • Zhengzhou, Henan, China, 450003
        • Henan Cancer Hospital
        • Contact:
    • Jiangsu
      • Nanjing, Jiangsu, China, 210029
        • Jiangsu Province 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

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Subjects voluntarily participate in clinical research;
  • Age ≥18 years old;
  • Eastern Cooperative Oncology Group (ECOG) score 0-2;
  • Examination evidence of initial diagnosis of MM according to IMWG diagnostic criteria;
  • Measurable lesions were present;
  • Subjects have received at least three previous lines of multiple myeloma therapy, each with at least one complete therapy cycle, unless the best response to the therapeutic regimen was documented as disease progression (PD confirmed according to IMWG criteria);
  • Expected survival ≥3 months;
  • Clinical laboratory values in the screening period meet criteria;

Exclusion Criteria:

  • Received previous therapy targeting GPRC5D and/or CD19 targets;
  • Prior antineoplastic therapy and meet exclusion criteria (before apheresis);
  • Subjects had Waldenstrom macroglobulinemia, POEMS syndrome, or primary AL amyloidosis at the time of screening.
  • Subjects who were positive for any of HBsAg, HBV DNA, HCV-Ab, HCV RNA, and HIV-Ab;
  • Life-threatening allergic reactions, hypersensitivity reactions, or intolerance to CAR-T cell formulations or their excipients, including DMSO, are known.
  • Serious underlying diseases were present;
  • Female subjects who were pregnant, breastfeeding, or planning to become pregnant while participating in this study or within 1 year of receiving study treatment.
  • Also enrolled in other clinical studies.

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
Intervention / Treatment
Experimental: LCAR-M61S and LCAR-M61D
Each subject will be given a single-dose LCAR-M61S or LCAR-M61D cells infusion at each dose level.
Biological: LCAR-M61S cells preparation

Biological:

LCAR-M61S or LCAR-M61D cells intravenous infusion; Prior to infusion of the LCAR-M61S and LCAR-M61D cell preparation, Subjects will receive a conditioning premedication regimen consisting of cyclophosphamide and fludarabine.

Other Names:
  • Cyclophosphamide
  • Fludarabine
Biological: LCAR-M61D cells preparation

Biological:

LCAR-M61S or LCAR-M61D cells intravenous infusion; Prior to infusion of the LCAR-M61S and LCAR-M61D cell preparation, Subjects will receive a conditioning premedication regimen consisting of cyclophosphamide and fludarabine.

Other Names:
  • Cyclophosphamide
  • Fludarabine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose-limiting toxicity (DLT) rate
Time Frame: From LCAR-M61S and LCAR-M61D cell preparations infusion (Day 1) until the 30th day of follow-up period, assessed up to 30 days
DLT was classified according to the NCI-CTCAE V5.0 toxicity evaluation criteria and ASTCT consensus classification within 30 days after dose infusion (D1-D30), which was considered by the investigator or collaborator to be reasonably related to LCAR-M61S or LCAR-M61D cell therapy.
From LCAR-M61S and LCAR-M61D cell preparations infusion (Day 1) until the 30th day of follow-up period, assessed up to 30 days
Incidence, severity, and type of treatment-emergent adverse events (TEAEs)
Time Frame: From the date of signing ICF to the date (2 years after LCAR-M61S and LCAR-M61D cell preparation infusion (Day 1)
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
From the date of signing ICF to the date (2 years after LCAR-M61S and LCAR-M61D cell preparation infusion (Day 1)
To determine the recommended dose for phase II clinical trials (RP2D)
Time Frame: Through the last subject of DLT exploration completion, about 2 years
RP2D established through accelerated titration design (ATD) and Bayesian Optimal Interval (BOIN) design
Through the last subject of DLT exploration completion, about 2 years
Maximum concentration (Cmax)
Time Frame: From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years
The maximum observed concentration of CAR positive T cells or transgene CAR copy number in peripheral blood.
From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years
Time to Cmax (Tmax)
Time Frame: From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years
The time it takes to reach the maximum concentration of CAR positive T cells or transgene CAR copy number in peripheral blood.
From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years
Time to the last observed concentration (Tlast)
Time Frame: From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years
The time it takes to reach the last observed concentration of CAR positive T cells or transgene CAR copy number in peripheral blood.
From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years
Area Under the Curve (AUC) of the concentration
Time Frame: From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years
The exposure of CAR positive T cells or transgene CAR copy number in peripheral blood experienced by the subject in a certain time interval.
From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years
According to International Myeloma Working Group (IMWG) efficacy criteria.ORR was defined as the proportion of patients with PR or better response after infusion of LCAR-M61S or LCAR-M61D cells.
From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years
Very Good Partial Response Rate（VGPR）
Time Frame: From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years
Proportion of subjects achieving VGPR according to IMWG criteria.
From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years
Complete response（CR）
Time Frame: From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years
Proportion of subjects achieving CR according to IMWG criteria.
From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years
Stringent complete response（sCR）
Time Frame: From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years
Proportion of subjects achieving sCR according to IMWG criteria.
From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years
Minimal residual disease (MRD) negative rate
Time Frame: From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression，assessed about 2 years
Proportion of subjects achieving minimal residual disease (MRD) negative rate according to IMWG criteria.
From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression，assessed about 2 years
Time-to-response（TTR）
Time Frame: From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years
According to International Myeloma Working Group (IMWG) efficacy criteria.TTR was defined as the interval from the date of the first infusion of the LCAR-M61S or LCAR-M61D cells preparation to the date of the first efficacy assessment for which the subject met all criteria for PR or better. Analyses were performed only in responders.
From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years
Duration of response（DOR）
Time Frame: From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years
According to International Myeloma Working Group (IMWG) efficacy criteria. DOR was defined as the time from the first documented response (PR or better response) to the first documented evidence of disease progression (as defined according to IMWG criteria) or death from any cause .
From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years
Progression-free survival（PFS）
Time Frame: From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years
According to International Myeloma Working Group (IMWG) efficacy criteria.PFS was defined as the interval from the date of the first infusion of the LCAR-M61S or LCAR-M61D cells preparation to the first documentation of disease progression (according to IMWG criteria) or death from any cause, whichever occurred first.
From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years
Overall survival（OS）
Time Frame: From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years
According to International Myeloma Working Group (IMWG) efficacy criteria.Overall survival (OS) was defined as the interval from the date of the first infusion of LCAR-M61S or LCAR-M61D cells preparation to death.
From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years
Occurrence rate of antidrug antibody
Time Frame: From LCAR-M61S or LCAR-M61D cells preparation infusion until the date of first documented progression or study completion，assessed about 2 years
Occurrence rate of LCAR-M61S or LCAR-M61D cells preparation ADA
From LCAR-M61S or LCAR-M61D cells preparation infusion until the date of first documented progression or study completion，assessed about 2 years

Collaborators and Investigators

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

Sponsor

The First Affiliated Hospital with Nanjing Medical University

Collaborators

Nanjing Legend Biotech Co.

Investigators

  • Principal Investigator: Lijuan Chen, The First Affiliated Hospital with Nanjing Medical 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 (Estimated)

July 1, 2024

Primary Completion (Estimated)

August 22, 2028

Study Completion (Estimated)

October 12, 2029

Study Registration Dates

First Submitted

June 6, 2024

First Submitted That Met QC Criteria

June 24, 2024

First Posted (Actual)

June 25, 2024

Study Record Updates

Last Update Posted (Actual)

June 28, 2024

Last Update Submitted That Met QC Criteria

June 27, 2024

Last Verified

June 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LB2401-0001

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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