A Study of LCAR-B38M CAR-T Cells, a Chimeric Antigen Receptor T-cell (CAR-T) Therapy Directed Against B-cell Maturation Antigen (BCMA) in Chinese Participants With Relapsed or Refractory Multiple Myeloma

Phase 2TerminatedNCT03758417

Nanjing Legend Biotech Co.123 enrolled

Overview

The purpose of this study is to evaluate the efficacy and safety of LCAR-B38M chimeric antigen receptor T (CAR-T) cells.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

123

Conditions

Multiple Myeloma

Interventions

LCAR-B38M CAR-T CellBIOLOGICAL

Participants will receive LCAR-B38M CAR-T cells as a single infusion which consists of autologous T lymphocytes transduced with LCAR-B38M, a lentiviral vector to express a chimeric antigen receptor targeting the human B cell maturation antigen (anti-BCMA CAR).

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Documented initial diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria * Measurable disease at Screening * Received at least 3 prior lines of treatment for multiple myeloma a) Undergone at least 1 complete cycle of treatment for each line, unless progressive disease (PD) was documented by IMWG criteria as the best response to the regimen * Received a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD) * Participant must have documented evidence of progressive disease based on investigator's determination of response consistent with IMWG criteria on or within 12 months of their last regimen. Non-responsive disease is defined as either failure to achieve minimal response or development of progressive disease (PD) while on therapy. Also, participants with documented evidence of PD disease (as above) within the previous 6 months and who are refractory or non-responsive to their most recent line of treatment afterwards are eligible * Eastern Cooperative Oncology Group (ECOG) Performance Status grade of 0 or 1 Exclusion Criteria: * Prior treatment with chimeric antigen receptor T (cells) CAR-T therapy directed at any target * Any therapy that is targeted to B-cell maturation antigen (BCMA) * The following cardiac conditions: a) New York Heart Association (NYHA) stage III or IV congestive heart failure b) Myocardial infarction or coronary artery bypass graft (CABG) 6 months prior to enrollment c) History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration d) History of severe non-ischemic cardiomyopathy e) Impaired cardiac function (left ventricular ejection fraction \[LVEF\] less than \[\<\]45%) as assessed by echocardiogram or multiple-gated acquisition (MUGA) scan (performed less than or equal to (\<=) 8 weeks of apheresis) * Have received a cumulative dose of corticosteroids equivalent to greater than or equal to(\>=)70 milligram (mg) of prednisone within 7 days prior to apheresis * Diagnosed or treated for invasive malignancy other than multiple myeloma, except: 1. Malignancy treated with curative intent and with no known active disease present for greater than or equal to (\>=) 2 years before enrollment; or 2. Adequately treated non-melanoma skin cancer without evidence of disease * Prior antitumor therapy with insufficient washout period * Toxicity from previous anticancer therapy must resolve to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy * Received either of the following: 1. An allogeneic stem cell transplant for multiple myeloma 2. An autologous stem cell transplant less than or equal to (\<=) 12 weeks before apheresis * Known active, or prior history of, central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma

Locations (11)

Peking University Third Hospital

Beijing, Beijing Municipality, China

Fujian Medical University Union hospital

Fuzhou, Fujian, China

Sun Yat -Sen University Cancer Center

Guandong, Guangzhou, China

Outcomes

Primary Outcomes

Overall Response Rate (ORR)

The ORR is defined as the percentage of participants who achieve at least a partial response (PR) or better according to international myeloma working group (IMWG) criteria.

Time frame: Minimum 2 years after LCAR-B38M chimeric antigen receptor T (CAR-T) infusion (Day 1)

Secondary Outcomes

Number of Participants With Adverse Events

An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.

Time frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)

Chimeric Antigen Receptor T (CAR-T) Positive Cell Concentration

Venous blood samples will be collected for measurement of CAR-T positive cellular concentration.

Time frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)

Transgene Levels of LCAR-B38M CAR-T Cells

Transgene Levels of LCAR-B38M CAR-T Cells using sensitive assay methods will be assessed.

Time frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)

Systemic Cytokine Concentrations

Serum cytokine concentrations such as Interleukin \[IL\]-6, IL-15, IL-10 will be measured for biomarker assessment.

Time frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)

Number of Participants With Anti- LCAR-B38M CAR-T Cell Antibodies

Number of participants with anti- LCAR-B38M CAR-T cell antibodies will be evaluated.

Time frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)

Data from ClinicalTrials.gov

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Nanjing Drum Tower Hospital

Nanjing, Jiangsu, China

Jiangsu Province Hospital

Nanjing, Jiangsu, China

Shanghai Changzheng Hospital

Shanghai, Shanghai Municipality, China

Ruijin Hospital, Shanghai Jiao Tong University

Shanghai, Shanghai Municipality, China

Shanghai Fourth People Hospital

Shanghai, Shanghai Municipality, China

The Second Affiliated Hospital of Xi'an Jiaotong University

Xi’an, Shanxi, China

West China Hospital, Sichuan University

Chengdu, Sichuan, China

...and 1 more locations

Percentage of Participants with Very Good Partial Response (VGPR) or Better Rate

The VGPR or better rate, defined as the percentage of participants achieving VGPR and complete response (CR) (including stringent complete response \[sCR\]) according to IMWG criteria during or after the study treatment. IMWG criteria for VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis, or greater than or equal to (\>=) 90 percent (%) reduction in serum Mprotein plus urine M-protein less than (\<) 100 milligram (mg)/24 hours, CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas and \<5% plasma cells (PCs) in bone marrow. sCR: CR plus normal free light chain (FLC) ratio, and absence of clonal PCs by immunohistochemistry (IHC), immunofluorescence for 2 to 4 color flow cytometry.

Time frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)

Percentage of Participants with Complete Response (CR)

Complete response is based on serum M-Protein and bone marrow assessments as per IMWG criteria.

Time frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)

Percentage of Participants with Negative Minimal Residual Disease (MRD)

Minimal residual disease negative rate is defined as the percentage of participants who achieve MRD negative status by the respective time point. MRD will be assessed by bone marrow 8-colored flow cytometry.

Time frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)

Percentage of Participants who Achieve Clinical Benefit

Clinical Benefit Rate is defined as the percentage of participants who achieve ORR (sCR + CR + VGPR + PR) and minimal response (MR) as per IMWG criteria.

Time frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)

Duration of Response (DOR)

Duration of response (DOR) will be calculated among responders (with a PR or better response) from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the IMWG criteria or death due to any cause, whichever occurs first.

Time frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)

Time to Response (TTR)

Time to response (TTR) is defined as the time between date of the initial infusion of LCAR-B38M CAR-T cells and the first efficacy evaluation that the participant has met all criteria for PR or better.

Time frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)

Progression-Free Survival (PFS)

PFS defined as time from date of initial infusion of LCAR-B38M CAR-T cells to date of first documented disease progression, defined in the IMWG criteria, or death due to any cause, whichever occurs first.

Time frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)

Overall survival (OS)

Overall survival (OS) is measured from the date of infusion of the LCAR-B38M CAR-T cells to the date of the participant's death.

Time frame: Mnimum 2 years after LCAR-B38M CART infusion (Day 1)

Levels of CAR-T cell Activation Markers

Levels of CAR-T cell Activation Markers like CD4+, CD8+, and CD25+ will be assessed. An evaluation of cell populations may be performed by flow cytometry.

Time frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)

Levels of LCAR-B38M CAR-T cell Expansion (proliferation)

Levels of LCAR-B38M CAR-T cell expansion (proliferation) will be reported.

Time frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)

Levels of LCAR-B38M CAR-T Persistence

Levels of LCAR-B38M CAR-T persistence will be evaluated via monitoring CAR-T positive cell counts and CART transgene levels.

Time frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)

Percentage of Participants with Stringent Complete Response (sCR)

Stringent Complete Response (sCR) is based on serum M-Protein and bone marrow assessments as per IMWG criteria for complete response(CR) plus normal free light chain (FLC) ratio, and absence of clonal PCs by immunohistochemistry(IHC), or 2 to 4 color flow cytometry.

Time frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)

Circulating Soluble B-Cell Maturation Antigen (sBCMA) Levels

Blood samples will be collected for measurement of sBCMA level.

Time frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)

Percent Reduction in BCMA Expression Cells

Percent reduction in BCMA Expression Cells will be measured.

Time frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)