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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
Wuhan Si'an Medical Technology Co., Ltd
Information provided by (Responsible Party):
MEI HENG, Wuhan Union Hospital, China

Brief Summary:
This is a single-center, open-label, single-arm study to evaluate the safety and efficacy of the bispecific CAR T cells targeting CS1 and BCMA in patients with relapsed or refractory multiple myeloma.

Condition or disease Intervention/treatment Phase
CS1+ or BCMA+ Multiple Myeloma Biological: Conditioning chemotherapy followed by CAR T cell infusion Phase 1

Detailed Description:
  • 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. 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).

Secondary Outcome Measures :
  1. 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).

  2. 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).

Other Outcome Measures:
  1. 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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

Each potential subject must meet all of the following criteria to be enrolled in the study:

  1. Aged 18-78 years old, males or females.
  2. Relapsed or refractory multiple myeloma according to IMWG diagnostic criteria.
  3. Received at least 2 prior lines of treatment for multiple myeloma, including a proteasome inhibitor and an immunomodulatory drug.
  4. Detectable MM cells in bone marrow by conventional morphologic methods or flow cytometry, and positive expression of CS1 or BCMA on MM cells as confirmed by immunohistochemistry or flow cytometry.
  5. Measurable diseases at screening as defined by any of the following:

    • Serum M-protein level ≥1.0g/dL;
    • Urine M-protein level ≥200mg/24 hours;
    • Serum immunoglobulin free light chain(FLC) ≥10 mg/dL provided abnormal FLC ratio.
  6. Recovery to grade 1 or baseline of toxicities due to prior treatment, excluding hematologic toxicities and toxicity of no clinical significance, like alopecia.
  7. ECOG Performance Status 0 ~ 2 (ECOG status of larger than 2 points caused by MM osteolytic destruction is accepted).
  8. Good organ function at screening as defined by any of the following:

    • AST and ALT ≤ 2.5×upper limit of normal (ULN);
    • Total bilirubin≤ 2.0×ULN;
    • Creatinine clearance ≥30 mL/min/1.73m2;
    • Ejection fraction of heart ≥50%, and no clinically significant abnormal ECG findings.
  9. Clinical laboratory values meeting the following criteria at screening:

    • Absolute Neutrophil Count(ANC) ≥1.0×10^9/L;
    • Platelets ≥30×10^9/L;
    • Absolute Lymphocyte Count ≥1.0×10^8/L;
    • Hemoglobin(Hb) ≥6.0g/dL.
  10. Women of childbearing potential must have a negative pregnancy test at screening.
  11. Patients with extramedullary lesions were eligible.
  12. Patients who received prior allogeneic or autologous stem cell transplantation at least three months before screening were eligible.
  13. Sign the informed consent voluntarily.

Exclusion Criteria:

Any potential subject who meets any of the following criteria will be excluded from participating in the study:

  1. Evidence of serious viral, bacterial, or uncontrolled systemic fungal infection.
  2. Seropositive for human immunodeficiency virus (HIV) antibody.
  3. Seronegative for hepatitis B antigen or a known history of hepatitis B.
  4. Hepatitis C (anti-hepatitis C virus [HCV] antibody positive or HCV-RNA quantitation positive) or a known history of hepatitis C.
  5. Systemic corticosteroid therapy of greater than 5 mg/day of prednisone or equivalent dose within 2 weeks prior to apheresis.
  6. Active autoimmune disease or a history of autoimmune disease within 3 years.
  7. The following cardiac conditions: Myocardial infarction or coronary artery bypass graft ≤6 months prior to enrollment; History of clinically significant ventricular arrhythmia or unexplained; New York Heart Association stage III or IV congestive heart failure.
  8. A history of epilepsy or other central nervous system diseases or altered mental status.
  9. Known life-threatening allergies, hypersensitivity, or intolerance to BM38 CAR T cells or relevant lymphodepleting regimens (cyclophosphamide and fludarabine).
  10. Pregnant or breast-feeding, or planning to become pregnant while enrolled in this study or within one year after receiving study treatment.
  11. Any uncontrolled diseases, other than multiple myeloma, that may lead to abnormal death.
  12. Being participating in other intervention studies.
  13. Other cases excluded by the Investigators.

Information from the National Library of Medicine

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

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Contact: Heng Mei, M.D., Ph.D 86-13986183871 hmei@hust.edu.cn
Contact: Chenggong Li 86-18868112136 chenggongli@hust.edu.cn

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China, Hubei
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Recruiting
Wuhan, Hubei, China, 430022
Contact: Heng Mei, M.D., Ph.D       hmei@hust.edu.cn   
Contact: Chenggong Li       chenggongli@hust.edu.cn   
Principal Investigator: Heng Mei, M.D., Ph.D         
Sponsors and Collaborators
Wuhan Union Hospital, China
Wuhan Si'an Medical Technology Co., Ltd
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Principal Investigator: Heng Mei, M.D., Ph.D Wuhan Union Hospital, China
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Responsible Party: MEI HENG, Proferssor, Cheif Doctor, Wuhan Union Hospital, China
ClinicalTrials.gov Identifier: NCT04662099    
Other Study ID Numbers: CS1+BCMA bispecific CART
First Posted: December 10, 2020    Key Record Dates
Last Update Posted: March 2, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases