Clinical Trial to Evaluate Zevor-cel (CT053) in Patients With Relapsed and/or Refractory Multiple Myeloma (LUMMICAR STUDY 2)

Study Overview
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Brief Summary
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A phase 1b/2, open label, multi-center, Clinical Study of Chimeric Antigen Receptor T Cells targeting BCMA in patients with relapsed and or refractory multiple myeloma.

Detailed Description
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This is an open label, multi-center, phase 1b/2 clinical trial to evaluate the safety and efficacy of autologous chimeric antigen receptor-B-cell maturation antigen (CAR-BCMA T cell; zevor-cel/CT053) in patients with relapsed and or refractory multiple myeloma. Phase 1b of the study will be dose escalation followed by an expansion cohort. After recommended Phase 2 dose is identified in Phase 1b, the enrollment of Phase 2 will start. Following consent, enrolled subjects will undergo a leukapheresis procedure to collect autologous mononuclear cells for manufacture of investigational drug product (zevor-cel). Following manufacture of the drug product, subjects will receive lymphodepletion prior to zevor-cel infusion. All subjects who complete the study, as well as those who withdraw from the study after receiving zevor-cel for reasons other than death or meeting the early termination criteria, will be asked to continue to undergo a 15-year long-term follow-up study.

Official Title
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Open Label, Multi-center, Phase 1b/2 Clinical Trial to Evaluate the Safety and Efficacy of Autologous CAR BCMA T Cells (CT053) in Patients With Relapsed and/or Refractory Multiple Myeloma (LUMMICAR STUDY 2)

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Biological: zevor-cel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntarily signed consent; Age of ≥ 18 and < 80 years; Received sufficient prior lines of myeloma therapy; Received treatment with at least one proteasome inhibitor, one IMiD and CD38 anti body. The patient must be refractory to the last line of therapy. The patients should have measurable disease per IMWG definition. Estimated life expectancy > 12 weeks; ECOG performance score 0-1; Patients should have reasonable CBC counts, renal and hepatic functions; Sufficient venous access for leukapheresis collection, and no other contraindications to leukapheresis; Women of childbearing age must undergo a serum pregnancy test with negative results before screening, and are willing to use effective and reliable method of contraception for at least 12 months after T cell infusion; Men must be willing to use effective and reliable method of contraception for at least 12 months after T cell infusion. Exclusion Criteria: Pregnant or lactating women; HIV, active hepatitis C virus (HCV), or active hepatitis B virus (HBV) infection; Any uncontrolled active infection; AEs from previous treatment that have not recovered; Patients who have had anti-BCMA therapy; Patients who have graft versus host disease (GvHD); Patients have received stem cell transplantation one year before leukapheresis; Patients have received any anti-cancer treatment before leukapheresis; Patients have received steroids before leukapheresis or lymphodepletion; Patients have plasma cell leukemia, Waldenström macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome or clinically significant symptomatic immunoglobulin light chain (AL) amyloidosis with evidence of end-organ damage; Patients have been administered live attenuated vaccine before leukapheresis or lymphodepletion; Patients allergic to Flu, Cy, tocilizumab, dimethyl sulfoxide (DMSO) or zevor-cel CAR BCMA T cell; Patients have clinical significant cardiac conditions that researchers believe that participating in this clinical trial may endanger the health of the patients; Patients have clinical significant pulmonary conditions; Patients are known to have active autoimmune diseases including but not limited to psoriasis, rheumatoid arthritis and other needs of long-term immunosuppressive therapy; Patients with second malignancies in addition to MM are not eligible; Patients have central nervous system (CNS) metastases or CNS involvement; Patients have significant neurologic disorders; Patients are unable or unwilling to comply with the requirements of clinical trial; Patients have received major surgery prior to leukapheresis or prior to lymphodepletion.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 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: CAR-BCMA T Cells<br>Phase 1b will include a dose escalation followed by an expansion cohort to determine the recommended dose for the expansion part. After recommended Phase 2 is determined, patients in Phase 2 will be treated. | Biological: zevor-cel<br>* A single autologous chimeric antigen receptor-B-cell maturation antigen (CAR-BCMA T cell) infusion<br>* Other names: CAR-BCMA T Cell Infusion;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment Related adverse events (AEs) | Incidence of Treatment Related AEs, AEs of special interest and serious adverse events (SAEs) | Day 1 - Month 60 | 
| Identification of Maximum Tolerated Dose (MTD) | Incidence of dose-limiting toxicities (DLTs) | Day 1 - Month 60 | 
| Objective response rate | Objective response rate (ORR) per IMWG by IRC read | Day 1 - Month 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate additional clinical efficacy outcomes with zevor-cel treatment in patients with rrMM | Disease-specific response criteria including, but not limited to: complete response (CR), MRD, very good partial response (VGPR), and partial response (PR) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma, Time to Response, Time to Progression, Progression Free Survival, best response and Overall Survival | Day 1 - Month 60 | 
| Determine the efficacy of zevor-cel treatment in patients with rrMM, by investigator assessment | ORR, DOR, FPS, OS, MRD, time to response, time to progression, best tumor response | Day 1 - Month 60 | 
| Evaluate zevor-cel PK profile | CAR transgene copy number, peak value, AUC, in vivo persistence | Day 1 - Month 60 | 
| Evaluate ADA profile | Percentage of patients with anti-zevor-cel drug antibodies | Day 1 - Month 60 | 
| Evaluate HRQoL in patients with rrMM from baseline up to study completion | Change from baseline in HRQoL as measured by EORTC QLQ-C30 and QLQ-MY20 | Day 1 - Month 60 | 
| Evaluate utilization of hospital resources | Duration of hospitalization and ICU | Day 1 - Month 60 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAR-T, Carcinoma, Carcinoma, Multiple Myeloma, CT053, zevor-cel