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CS1+ or BCMA+ Multiple MyelomaPhase 1NCT04662099

T Cells Expressing a Bispecific CAR Targeting CS1 and BCMA in Relapsed/Refractory Multiple Myeloma

A Phase 1 study testing Conditioning chemotherapy followed by CAR T cell infusion in people with CS1+ or BCMA+ Multiple Myeloma, run by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
CS1+ or BCMA+ Multiple Myeloma
What is being tested?
Conditioning chemotherapy followed by CAR T cell infusion
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteChina
Study dates
25 Mar 2020to 30 Dec 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Each potential subject must meet all of the following criteria to be enrolled in the study:
  • Aged 18-78 years old, males or females.
  • Relapsed or refractory multiple myeloma according to IMWG diagnostic criteria.
  • Received at least 2 prior lines of treatment for multiple myeloma, including a proteasome inhibitor and an immunomodulatory drug.
  • 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.
  • Measurable diseases at screening as defined by any of the following:
Show all 25Show fewer
  • 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.
  • Recovery to grade 1 or baseline of toxicities due to prior treatment, excluding hematologic toxicities and toxicity of no clinical significance, like alopecia.
  • ECOG Performance Status 0 ~ 2 (ECOG status of larger than 2 points caused by MM osteolytic destruction is accepted).
  • 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.
  • 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.
  • Women of childbearing potential must have a negative pregnancy test at screening.
  • Patients with extramedullary lesions were eligible.
  • Patients who received prior allogeneic or autologous stem cell transplantation at least three months before screening were eligible.
  • Sign the informed consent voluntarily.

Who cannot join

  • Any potential subject who meets any of the following criteria will be excluded from participating in the study:
  • Evidence of serious viral, bacterial, or uncontrolled systemic fungal infection.
  • Seropositive for human immunodeficiency virus (HIV) antibody.
  • Seronegative for hepatitis B antigen or a known history of hepatitis B.
  • Hepatitis C (anti-hepatitis C virus [HCV] antibody positive or HCV-RNA quantitation positive) or a known history of hepatitis C.
  • Systemic corticosteroid therapy of greater than 5 mg/day of prednisone or equivalent dose within 2 weeks prior to apheresis.
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  • Active autoimmune disease or a history of autoimmune disease within 3 years.
  • 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.
  • A history of epilepsy or other central nervous system diseases or altered mental status.
  • Known life-threatening allergies, hypersensitivity, or intolerance to CAR-T cells or relevant lymphodepleting regimens (cyclophosphamide and fludarabine).
  • Pregnant or breast-feeding, or planning to become pregnant while enrolled in this study or within one year after receiving study treatment.
  • Any uncontrolled diseases, other than multiple myeloma, that may lead to abnormal death.
  • Being participating in other intervention studies.
  • Other cases excluded by the Investigators.

Trial locations and contacts

1 site in 1 country.

Heng Mei, M.D., Ph.D contact

86-13986183871

hmei@hust.edu.cn

Chenggong Li contact

86-18868112136

chenggongli@hust.edu.cn

China1 site, 1 recruiting

  • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

    Wuhan, Hubei, 430022

    Heng Mei, M.D., Ph.D, hmei@hust.edu.cn

    Chenggong Li, chenggongli@hust.edu.cn

    Recruiting

Other trials in China

About this study

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

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.

Read the 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.
Being tested
Conditioning chemotherapy followed by CAR T cell infusion

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Conditioning chemotherapy followed by CAR T cell infusionBiological

    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.

Study groups in NCT04662099
Study groupRoleWhat they receive
Conditioning chemotherapy plus CAR T cells infusionExperimentalNot described
Receives: Biological: Conditioning chemotherapy followed by CAR T cell infusion

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of Treatment-related Adverse Events

    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).

    Measured: within 2 years after infusion

Secondary outcomes (2)

  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

    OR and CRR will be assessed from CAR T cell infusion to death or last follow-up (censored).

    Measured: 2 years after infusion

  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

    OS, PFS and DOR will be assessed from CAR T cell infusion to death or last follow-up (censored).

    Measured: 2 years after infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Dec 2020
  2. Study start25 Mar 2020
  3. Primary completion30 Dec 2023 (estimated)
  4. Study completion30 Dec 2023 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
24 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04662099
Sponsor's protocol ID
CS1+BCMA bispecific CART
Status last verified
Aug 2023
First submitted
3 Dec 2020
Last updated
16 Aug 2023
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Zah E, Nam E, Bhuvan V, Tran U, Ji BY, Gosliner SB, Wang X, Brown CE, Chen YY. Systematically optimized BCMA/CS1 bispecific CAR-T cells robustly control heterogeneous multiple myeloma. Nat Commun. 2020 May 8;11(1):2283. doi: 10.1038/s41467-020-16160-5.

    PubMed 32385241

  • Mikkilineni L, Kochenderfer JN. CAR T cell therapies for patients with multiple myeloma. Nat Rev Clin Oncol. 2021 Feb;18(2):71-84. doi: 10.1038/s41571-020-0427-6. Epub 2020 Sep 25.

    PubMed 32978608

  • Li C, Xu J, Luo W, Liao D, Xie W, Wei Q, Zhang Y, Wang X, Wu Z, Kang Y, Zheng J, Xiong W, Deng J, Hu Y, Mei H. Bispecific CS1-BCMA CAR-T cells are clinically active in relapsed or refractory multiple myeloma. Leukemia. 2024 Jan;38(1):149-159. doi: 10.1038/s41375-023-02065-x. Epub 2023 Oct 17.

    PubMed 37848634

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Conditioning chemotherapy followed by CAR T cell infusion in people with CS1+ or BCMA+ Multiple Myeloma, run by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 16 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Heng Mei, M.D., Ph.D (86-13986183871, hmei@hust.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Treatment-related Adverse Events (time frame: within 2 years after infusion). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04662099, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Aug 2023.

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