CAR T cells targeting CS1 and BCMA for multiple myeloma

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 study is testing a new type of CAR T cell therapy that targets two proteins to see if it can help people with relapsed or hard-to-treat multiple myeloma feel better and stay in remission longer.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Wuhan Union Hospital, China (Academic / other)
• Drugs / interventions: CAR-T, cyclophosphamide, fludarabine, prednisone, CAR T, chimeric antigen receptor
• Locations: 1 site (Wuhan, Hubei)
• Trial ID: NCT04662099 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and efficacy of bispecific CAR T cells that target both CS1 and BCMA in patients with relapsed or refractory multiple myeloma. The approach involves conditioning chemotherapy followed by the infusion of these engineered T cells, which have shown potent cytotoxicity against multiple myeloma cells in preclinical models. The goal is to improve patient outcomes by reducing relapse rates associated with single-target therapies. The study is conducted at a single center and is open-label, allowing for direct observation of treatment effects.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-78 with relapsed or refractory multiple myeloma who have received at least two prior lines of treatment.

Not a fit: Patients who have not been previously treated for multiple myeloma or those with other hematological malignancies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with relapsed or refractory multiple myeloma.

How similar studies have performed: Other studies have shown promising results with BCMA-targeted therapies, but this bispecific approach is relatively novel.

Eligibility criteria

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 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.

Where this trial is running

Wuhan, Hubei

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (Recruiting)

Study contacts

• Principal investigator: Heng Mei, M.D., Ph.D — Wuhan Union Hospital, China
• Study coordinator: Heng Mei, M.D., Ph.D

Conditions CS1+ or BCMA+ Multiple Myeloma