This investigator-initiated, exploratory clinical trial is designed to evaluate the feasibility, safety, and preliminary antitumor activity of autologous CS1-targeted chimeric antigen receptor T (CAR-T) cells in adults with relapsed or refractory multiple myeloma (MM). Multiple myeloma is a hematologic malignancy characterized by the clonal proliferation of plasma cells. Despite advances in treatment, patients with relapsed or refractory disease often have limited therapeutic options after multiple lines of therapy. CS1, also known as signaling lymphocytic activation molecule family member 7 (SLAMF7; CD319), is highly expressed on myeloma cells throughout the course of disease and has been investigated as a therapeutic target. The clinical activity of the anti-SLAMF7 monoclonal antibody elotuzumab supports the rationale for targeting this antigen. CS1-targeted CAR-T cell therapy is being investigated as a potential treatment option for patients with relapsed or refractory multiple myeloma. This is an open-label, single-center, non-randomized, Phase I dose-escalation study evaluating autologous CS1-targeted CAR-T cells. The primary objectives are to evaluate the feasibility and safety of autologous CS1-targeted CAR-T cell therapy and to assess its preliminary antitumor activity. Eligible participants are adults with relapsed or refractory multiple myeloma diagnosed according to the International Myeloma Working Group (IMWG) criteria who have received multiple prior lines of therapy, have measurable disease, and meet protocol-defined organ function requirements.
This investigator-initiated Phase 1 clinical study is designed to evaluate the feasibility, safety, tolerability, and preliminary antitumor activity of autologous CS1-targeted chimeric antigen receptor T (CAR-T) cells in adults with relapsed or refractory multiple myeloma (MM). Multiple myeloma is a hematologic malignancy characterized by the clonal proliferation of plasma cells. Although treatment options for multiple myeloma have expanded, patients with relapsed or refractory disease may develop resistance to available therapies and have limited treatment options. Cellular immunotherapies directed against antigens expressed on malignant plasma cells represent a potential therapeutic approach for this patient population. CS1, also known as signaling lymphocytic activation molecule family member 7 (SLAMF7; CD319), is a cell-surface antigen that is highly expressed on plasma cells and multiple myeloma cells. The expression of CS1 on malignant plasma cells provides a rationale for investigating CS1-directed CAR-T cell therapy. Autologous CS1-targeted CAR-T cells are genetically modified T lymphocytes designed to recognize CS1-expressing cells and mediate an immune response against target cells. This is a single-center, single-group, open-label, non-randomized Phase 1 study without a control arm. The study uses a dose-escalation design to evaluate different dose levels of autologous CS1-targeted CAR-T cells. Participants receive the investigational treatment according to the protocol-defined dose-escalation scheme. The investigational treatment consists of a single infusion of autologous CS1-targeted CAR-T cells. Participants undergo collection of autologous T cells for manufacture of the investigational CAR-T cell product. Once the CAR-T-cell product is ready, participants receive a single infusion of CS1-targeted CAR-T cells at the assigned dose level. Participants are subsequently monitored according to the study protocol for treatment-related adverse events, tolerability, and clinical and laboratory findings. The primary purpose of the dose-escalation portion of the study is to characterize the safety and tolerability of CS1-targeted CAR-T cell therapy across the planned dose levels. The study will also provide preliminary information regarding the antitumor activity of the investigational treatment. Disease assessments and safety evaluations will be conducted according to protocol-defined procedures and criteria. The study is intended to generate preliminary clinical evidence regarding the feasibility, safety, tolerability, and potential antitumor activity of autologous CS1-targeted CAR-T cell therapy in patients with relapsed or refractory multiple myeloma. The findings may provide information to support further clinical investigation of CS1-targeted CAR-T cell therapy in this patient population.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
Infusion of CS1 CAR-T cell product
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Tianjin, China
Number of Participants With Dose-Limiting Toxicities (DLTs) Within 28 Days After Autologous CS1 CAR-T Cell Infusion
DLT is defined as a treatment-related adverse event or laboratory abnormality occurring after CS1 CAR-T cell infusion that meets protocol-defined criteria and is not attributable to the underlying disease, disease progression, concomitant disease, or concomitant medication. Hematologic DLT is non-disease-related Grade 4 toxicity lasting more than 30 days, excluding lymphopenia. Non-hematologic DLT is treatment-related Grade ≥3 toxicity that does not decrease to Grade ≤1 or baseline within 14 days despite appropriate management. Protocol-specified exceptions apply. The number and percentage of participants with DLTs will be summarized by CS1 CAR-T cell dose level.
Time frame: From the first CS1 CAR-T cell infusion through Day 28 after the first infusion
Number of Participants With Treatment-Related Adverse Events Within 28 Days After Autologous CS1 CAR-T Cell Infusion
Treatment-related adverse events will be assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE). The number and percentage of participants experiencing treatment-related adverse events will be summarized by severity grade and relationship to CS1 CAR-T cell infusion during the protocol-defined 28-day DLT assessment period.
Time frame: From the first CS1 CAR-T cell infusion through Day 28 after infusion
Objective Response Rate (ORR) According to the International Myeloma Working Group (IMWG) 2016 Criteria
ORR is defined as the percentage of participants achieving a best overall response of partial response (PR), minimal response (MR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR), according to the IMWG 2016 response criteria. ORR will be summarized descriptively with the corresponding 95% confidence interval.
Time frame: From Day 28 after first infusion through Month 24 after infusion
Complete Response Rate (sCR + CR) According to the International Myeloma Working Group (IMWG) 2016 Criteria
Complete response rate is defined as the percentage of participants achieving a best overall response of stringent complete response (sCR) or complete response (CR), according to the IMWG 2016 response criteria. CR requires negative serum and urine immunofixation, disappearance of soft-tissue plasmacytomas, and \<5% plasma cells in bone marrow. sCR additionally requires a normal serum free light-chain ratio and absence of clonal plasma cells in bone marrow.
Time frame: From Day 28 after first infusion through Month 24 after infusion
Time to Response (TTR) According to the International Myeloma Working Group (IMWG) 2016 Criteria
TTR is defined as the time from the first CS1 CAR-T cell infusion to the first documented response of PR or better according to the IMWG 2016 criteria. TTR will be summarized descriptively among participants who achieve a response.
Time frame: From first infusion through Month 24 after infusion
Duration of Response (DOR) According to the International Myeloma Working Group (IMWG) 2016 Criteria
DOR is defined as the time from the first documented response of PR or better according to the IMWG 2016 criteria to the first documented disease progression or death from any cause, whichever occurs first. Participants without progression or death will be censored at the date of the last disease assessment.
Time frame: From first documented response through Month 24 after infusion
Progression-Free Survival (PFS) After CS1 CAR-T Cell Infusion
PFS is defined as the time from the first CS1 CAR-T cell infusion to the first documented disease progression according to the IMWG 2016 criteria or death from any cause, whichever occurs first. Participants without documented progression or death will be censored at the date of the last adequate disease assessment. PFS will be estimated using the Kaplan-Meier method.
Time frame: From first infusion through Month 24 after infusion
Overall Survival (OS) After CS1 CAR-T Cell Infusion
OS is defined as the time from the first CS1 CAR-T cell infusion to death from any cause. Participants who are alive at the last known follow-up will be censored on the date they were last known to be alive. OS will be estimated using the Kaplan-Meier method.
Time frame: From first infusion through Month 24 after infusion
Disease Control Rate (DCR) According to the International Myeloma Working Group (IMWG) 2016 Criteria
DCR is defined as the percentage of participants achieving a best overall response of minimal response (MR), partial response (PR), very good partial response (VGPR), complete response (CR), stringent complete response (sCR), or stable disease (SD), according to the IMWG 2016 criteria. DCR will be summarized descriptively with the corresponding 95% confidence interval.
Time frame: From Day 28 after first infusion through Month 24 after infusion
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