Clinical trial NCT03090659: LCAR-B38M Cells in Treating Relapsed/Refractory (R/R) Multiple Myeloma
Official title: A Clinical Study of Legend Biotech BCMA-chimeric Antigen Receptor Technology in Treating Relapsed/Refractory (R/R) Multiple Myeloma Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Refractory or Relapsed Multiple Myeloma
Keywords: multiple myeloma
BCMA
CAR-T
Lead sponsor: Nanjing Legend Biotech Co.
Sponsor class: INDUSTRY
Collaborators: name: Second Affiliated Hospital of Xi'an Jiaotong University
name: Ruijin Hospital
name: Jiangsu Provincial People's Hospital
name: Shanghai Changzheng Hospital
First posted: 2017-03-27
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Occurrence of treatment related adverse events as assessed by CTCAE v4.0
timeFrame: Day 1-30 days after injection
Secondary outcomes:
measure: Anti-myeloma responses to LCAR-B38M cell treatment
timeFrame: Day 1-36 months after three split doses
measure: Anti-myeloma responses to LCAR-B38M cell treatment
timeFrame: Day 1-36 months after three split doses
Other outcomes:
Locations:
Study officials:
References:
citation: 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.
citation: 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.