T Cells Expressing a Bispecific CAR Targeting CS1 and BCMA in Relapsed/Refractory Multiple Myeloma
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|ClinicalTrials.gov Identifier: NCT04662099|
Recruitment Status : Recruiting
First Posted : December 10, 2020
Last Update Posted : March 2, 2022
|Condition or disease||Intervention/treatment||Phase|
|CS1+ or BCMA+ Multiple Myeloma||Biological: Conditioning chemotherapy followed by CAR T cell infusion||Phase 1|
- Multiple myeloma(MM) is one of the most common hematological malignancies with substantial morbidity and mortality.
- In recent years, several new therapies have prolonged survival of patients with MM, but it is still an incurable malignancy of plasma cells.
- B-cell maturation antigen (BCMA) is expressed by normal and malignant plasma cells and a small subset of B cells. This specific expression pattern makes BCMA an ideal target antigen for immunotherapies in MM.
- BCMA-targeted chimeric antigen receptor (CAR) T cells have exhibited significant efficacy in MM, but relapse due to single-target escape or poor in vivo persistence has been reported.
- Dual-targets or sequential infusion have been proposed to reduce relapse and improve outcomes post BCMA-specific CAR T therapies.
- CS1 is expressed on pro-B cells and plasma cells especially malignant ones and some evidence suggests it plays a role in stromal cell interaction in the BM tumour microenvironment.
- We have constructed a bispecific CAR containing anti-CS1 single chain variable region (scFv) and an anti-BCMA scFv in 4-1BB-containing second-generation formats.
- The bispecific CAR T cells have exhibited potent cytotoxicity in various BCMA+ or/and CS1+ MM cells and can effectively eradicate MM cells in xenograft mice models.
- This study aims to evaluate prelimary safety and efficacy of the CS1&BCMA CAR T cells in patients with relapsed or refractory MM.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||Safety and Efficacy of the Bispecific CAR T Therapy Targeting CS1 and BCMA in Patients With Relapsed/ Refractory Multiple Myeloma: a Single-center, Open-label, Single-arm Clinical Study|
|Actual Study Start Date :||March 25, 2020|
|Estimated Primary Completion Date :||December 30, 2022|
|Estimated Study Completion Date :||December 30, 2023|
|Experimental: Conditioning chemotherapy plus CAR T cells infusion||
Biological: Conditioning chemotherapy followed by CAR T cell infusion
Conditioning chemotherapy: Cyclophosphamide 250 mg/m^2 and fludarabine 30 mg/m^2 IV infusion on days -5, -4, and -3 CAR T cells infusion: 0.75x10^6-3.0X10^6 CAR+ T cells per kg of recipient bodyweight. if DLTs don't occur at the dose of 3.0X10^6 CAR+ T cells per kg, the investigators will discuss whether to try higher dose.
- Incidence of Treatment-related Adverse Events [ Time Frame: within 2 years after infusion ]Therapy-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0).
- Overall response rate(ORR) and complete response rate(CRR) of administering T cells Expressing a bispecific CAR Targeting CS1 and BCMA in Relapsed/Refractory Multiple Myeloma [ Time Frame: 2 years after infusion ]OR and CRR will be assessed from CAR T cell infusion to death or last follow-up (censored).
- Overall survival(OS), duration of Response(DOR), progress-free survival(PFS) of administering T cells Expressing a bispecific CAR Targeting CS1 and BCMA in Relapsed/Refractory Multiple Myeloma [ Time Frame: 2 years after infusion ]OS, PFS and DOR will be assessed from CAR T cell infusion to death or last follow-up (censored).
- In vivo expansion and survival of CS1&BCMA bispecific CAR T cells [ Time Frame: 2 years after infusion ]In vivo (bone marrow and peripheral blood) rate and quantity will be determined by using flow cytometry and qPCR.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04662099
|Contact: Heng Mei, M.D., Ph.Demail@example.com|
|Contact: Chenggong Lifirstname.lastname@example.org|
|Union Hospital, Tongji Medical College, Huazhong University of Science and Technology||Recruiting|
|Wuhan, Hubei, China, 430022|
|Contact: Heng Mei, M.D., Ph.D email@example.com|
|Contact: Chenggong Li firstname.lastname@example.org|
|Principal Investigator: Heng Mei, M.D., Ph.D|
|Principal Investigator:||Heng Mei, M.D., Ph.D||Wuhan Union Hospital, China|