LCAR-B38M Cells in Treating Relapsed/Refractory (R/R) Multiple Myeloma

NCT ID: NCT03090659

Last Updated: 2023-06-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-02
• Study Completion Date: 2023-12-31

Brief Summary

This is a single arm, open-label, multi-center, phase 1/2 study, to determine the safety and efficacy of LCAR-B38M CAR-T cells in treating patients diagnosed with refractory/relapsed multiple myeloma (r/r MM).

Detailed Description

Multiple myeloma (MM) is a usually incurable malignancy of plasma cells. Current therapies for multiple myeloma often cause remissions, but nearly all patients eventually relapse and die, an clear unmet clinical needs. As early as mid-2014, the investigators have started to develop a series of proprietary CAR-T products to target B cell maturation antigen (BCMA), a cell surface molecule which the investigator believes to be a desirable target antigen for multiple myeloma. All pre-clinical data and CMC data for LCAR-B38M CAR-T cell technology has been established by mid-2015 and a phase I proof-of-concept clinical trial has been planned since then.

Conditions

Refractory or Relapsed Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

LCAR-B38M treatment group

r/r multiple myeloma patients be treated with a split doses of LCAR-B38M cells. Total dose of 0.5-5 millions /kg cells will be administered at day 0, day 2 and day 6 by split dose (20%, 30% and 50% respectively).

Group Type: EXPERIMENTAL

LCAR-B38M CAR-T cell injection

Intervention Type: BIOLOGICAL

Interventions

LCAR-B38M CAR-T cell injection

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Patients must have a confirmed prior diagnosis of active multiple myeloma as defined by the updated IMWG criteria.
• Patients with refractory multiple myeloma. Clear BCMA expression must be detected on malignant plasma cells from either bone marrow or a plasmacytoma by flow cytometry or immunohistochemistry.
• Refractory disease：1) At least 3 prior regimens, which must at least have contained bortezomi. or 2) other circumstances identified by clinical doctors.
• Relapse criteria in NCCN clinical practice guidelines in Oncology: Multiple Myeloma (2016.V2)

Exclusion Criteria

• Women of child-bearing potential or who are pregnant or breastfeeding.
• Have any active and uncontrolled infection: hepatitis B, hepatitis C, HIV, or other fatal viral and bacterial infection.
• Systemic corticosteroid steroid therapy of greater than 5 mg/day of prednisone or equivalent dose of another corticosteroid are not allowed within 2 weeks prior to either the required leukapheresis or the initiation of the conditioning chemotherapy regimen.
• Patients with any uncontrolled intercurrent illness or serious uncontrolled medical disorder.
• Patients with CNS metastases or symptomatic CNS involvement (including cranial neuropathies or mass lesions and spinal cord compression).
• History of allogeneic stem cell transplantation. Have active acute or chronic graft-versus-host-disease (GVHD), or require immunosuppressant medications for GVHD, within 6 months of enrollment.
• Patients with active autoimmune skin diseases such as psoriasis or other active autoimmune diseases such as rheumatoid arthritis.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Second Affiliated Hospital of Xi'an Jiaotong University

OTHER

Sponsor Role: collaborator

Ruijin Hospital

OTHER

Sponsor Role: collaborator

Jiangsu Provincial People's Hospital

OTHER

Sponsor Role: collaborator

Shanghai Changzheng Hospital

OTHER

Sponsor Role: collaborator

Nanjing Legend Biotech Co.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

References

Xu J, Wang BY, Yu SH, Chen SJ, Yang SS, Liu R, Chen LJ, Hou J, Chen Z, Zhao WH, He AL, Mi JQ, Chen SJ. Long-term remission and survival in patients with relapsed or refractory multiple myeloma after treatment with LCAR-B38M CAR T cells: 5-year follow-up of the LEGEND-2 trial. J Hematol Oncol. 2024 Apr 24;17(1):23. doi: 10.1186/s13045-024-01530-z.

Reference Type: DERIVED

PMID: 38659046 (View on PubMed)

Palmer S, Lin Y, Martin TG, Jagannath S, Jakubowiak A, Usmani SZ, Buyukkaramikli N, Phelps H, Slowik R, Pan F, Valluri S, Pacaud L, Jackson G. Extrapolation of Survival Data Using a Bayesian Approach: A Case Study Leveraging External Data from Cilta-Cel Therapy in Multiple Myeloma. Oncol Ther. 2023 Sep;11(3):313-326. doi: 10.1007/s40487-023-00230-x. Epub 2023 Jun 4.

Reference Type: DERIVED

PMID: 37270762 (View on PubMed)

Zhao WH, Wang BY, Chen LJ, Fu WJ, Xu J, Liu J, Jin SW, Chen YX, Cao XM, Yang Y, Zhang YL, Wang FX, Zhang PY, Lei B, Gu LF, Wang JL, Zhang H, Bai J, Xu Y, Zhu H, Du J, Jiang H, Fan XH, Li JY, Hou J, Chen Z, Zhang WG, Mi JQ, Chen SJ, He AL. Four-year follow-up of LCAR-B38M in relapsed or refractory multiple myeloma: a phase 1, single-arm, open-label, multicenter study in China (LEGEND-2). J Hematol Oncol. 2022 Jul 6;15(1):86. doi: 10.1186/s13045-022-01301-8.

Reference Type: DERIVED

PMID: 35794616 (View on PubMed)

Zhao WH, Liu J, Wang BY, Chen YX, Cao XM, Yang Y, Zhang YL, Wang FX, Zhang PY, Lei B, Gu LF, Wang JL, Yang N, Zhang R, Zhang H, Shen Y, Bai J, Xu Y, Wang XG, Zhang RL, Wei LL, Li ZF, Li ZZ, Geng Y, He Q, Zhuang QC, Fan XH, He AL, Zhang WG. A phase 1, open-label study of LCAR-B38M, a chimeric antigen receptor T cell therapy directed against B cell maturation antigen, in patients with relapsed or refractory multiple myeloma. J Hematol Oncol. 2018 Dec 20;11(1):141. doi: 10.1186/s13045-018-0681-6.

Reference Type: DERIVED

PMID: 30572922 (View on PubMed)

Other Identifiers

LCAR-B38M

Identifier Type: -

Identifier Source: org_study_id