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

NCT06472479 | Not Yet Recruiting

• 1 other identifier: LB2401-0001
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Relapsed/Refractory Multiple Myeloma

Keywords

Multiple myeloma; Relapsed/Refractory multiple myeloma

Outcome Measures

Primary Outcomes (7)

• Dose-limiting toxicity (DLT) rate

  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)

  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)

  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)

  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)

  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)

  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

  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 Outcomes (10)

• Objective Response Rate (ORR)

  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）

  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）

  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）

  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

  From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression，assessed about 2 years

Study Arms (1)

LCAR-M61S and LCAR-M61D

EXPERIMENTAL

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-M61D cells preparation

Interventions

LCAR-M61S cells preparation BIOLOGICAL

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.

Also known as: Cyclophosphamide, Fludarabine

LCAR-M61S and LCAR-M61D

LCAR-M61D cells preparation BIOLOGICAL

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.

Also known as: Cyclophosphamide, Fludarabine

LCAR-M61S and LCAR-M61D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• Received previous therapy targeting GPRC5D and/or CD19 targets;
• 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.

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead
• Nanjing Legend Biotech Co.: collaborator

Study Sites (4)

Anhui Cancer Hospital

Hefei, Anhui, 230031, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, 450003, China

Location

Jiangsu Province Hospital

Nanjing, Jiangsu, 210029, China

Location

Beijing Gobroad Hospital

Beijing, 102206, China

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Lijuan Chen

  The First Affiliated Hospital with Nanjing Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lijuan Chen

CONTACT

15850521836; chenljb@126.com

Xuxing Shen

CONTACT

15720803161; ruxiaoguo1992@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Single Group Assignment \& Two-cohort; LCAR-M61S and LCAR-M61D cells preparation intravenous infusion; Pretreatment of cyclophosphamide and fludarabine.

Study Record Dates

• First Submitted: June 6, 2024
• First Posted: June 25, 2024
• Study Start: July 1, 2024
• Primary Completion (Estimated): August 22, 2028
• Study Completion (Estimated): October 12, 2029
• Last Updated: June 28, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)