LCAR-B4822M-02 Cells in Treating Relapsed/Refractory (R/R) Multiple Myeloma

Study Overview
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Brief Summary
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This is a single arm, open-label, phase 1 study, to determine the safety and efficacy of LCAR-B4822M CAR-T cells in treating patients diagnosed with refractory/relapsed multiple myeloma (r/r MM).

Detailed Description
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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, there is an unmet clinical needs for these patients. B-cell maturation antigen (BCMA) is a protein expressed by normal plasma cells and the malignant plasma cells of multiple myeloma, and it was supposed to be a promising target for r/r MM.

Official Title
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LCAR-B4822M-02 Cells in Treating Relapsed/Refractory (R/R) Multiple Myeloma

Conditions
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Refractory or Relapsed Multiple Myeloma

Intervention / Treatment
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* Drug: LCAR-B4822M CAR-T Cell Immunotherapy


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 73 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LCAR-B4822M treatment group<br>r/r multiple myeloma patients will be treated with LCAR-B4822M CAR-T cells with a escalation approach, 0.5x10^6- 2.0x10^6 CAR-T cells/kg. | Drug: LCAR-B4822M CAR-T Cell Immunotherapy<br>* Patients will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of CAR-T cells. After a pre-treatment lymphodepletion therapy, patients will receive the LCAR-B4822M CAR-T Cell Immunotherapy by intravenous injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of treatment related adverse events | Assessed by CTCAE v4.0 | Day 1-30 days after injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-myeloma responses to LCAR-B4822M cell treatment | by measuring the changes of aberrant immunoglobulin in serum | Day 1-36 months after injection | 
| Anti-myeloma responses to LCAR-B38M cell treatment | multiple myeloma cells in bone marrow | Day 1-36 months after injection |