LCAR-B38M Cells in Treating Relapsed/Refractory (R/R) Multiple Myeloma (LEGEND-2)

• ClinicalTrials.gov Identifier: NCT03090659
• Recruitment Status: Unknown
• First Posted: March 27, 2017
• Last Update Posted: September 2, 2021
• Sponsor: Nanjing Legend Biotech Co.
• Collaborators: Second Affiliated Hospital of Xi'an Jiaotong University; Ruijin Hospital; Jiangsu Provincial People's Hospital; Shanghai Changzheng Hospital
• Information provided by (Responsible Party): Nanjing Legend Biotech Co.

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Refractory or Relapsed Multiple Myeloma	Biological: LCAR-B38M CAR-T cell injection	Phase 1; Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Clinical Study of Legend Biotech BCMA-chimeric Antigen Receptor Technology in Treating Relapsed/Refractory (R/R) Multiple Myeloma Patients
• Actual Study Start Date: October 2, 2015
• Estimated Primary Completion Date: December 31, 2021
• Estimated Study Completion Date: December 31, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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).	Biological: LCAR-B38M CAR-T cell injection

Outcome Measures

Primary Outcome Measures :

1. Occurrence of treatment related adverse events as assessed by CTCAE v4.0 [ Time Frame: Day 1-30 days after injection ]
   >= Grade 1 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to study treatment

Secondary Outcome Measures :

1. Anti-myeloma responses to LCAR-B38M cell treatment [ Time Frame: Day 1-36 months after three split doses ]
   by measuring the changes of aberrant immunoglobulin in serum
2. Anti-myeloma responses to LCAR-B38M cell treatment [ Time Frame: Day 1-36 months after three split doses ]
   multiple myeloma cells in bone marrow.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

No Contacts or Locations Provided

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

• Responsible Party: Nanjing Legend Biotech Co.
• ClinicalTrials.gov Identifier: NCT03090659
• Other Study ID Numbers: LCAR-B38M
• First Posted: March 27, 2017
• Last Update Posted: September 2, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Nanjing Legend Biotech Co.:

multiple myeloma; BCMA; CAR-T

Additional relevant MeSH terms:

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