Multiple Myeloma, Refractory
Conditions
Keywords
CAR-NK Therapy, Anti-BCMA
Brief summary
Immunotherapy has shown promise in the treatment of hematological malignancies, including multiple myeloma. One approach is CAR-NK cell therapy, which involves genetically modifying natural killer (NK) cells to target specific cancer antigens. While CAR-NK therapy offers advantages over CAR-T therapy, such as reduced immune system reactions and lower production time and cost, challenges remain in terms of antitumor efficacy and the tumor microenvironment. Preclinical and early clinical studies have targeted various antigens, including BCMA, with CAR-NK cells in multiple myeloma. To further investigate the potential of BCMA-targeted CAR-NK cell therapy, this study aims to evaluate its safety and determine the maximum tolerated dose (MTD) in patients who have not responded to standard therapy.
Interventions
BIOLOGICALAnti-BCMA CAR-NK
Ten eligible patients with relapsed refractory multiple myeloma will be enrolled based on inclusion criteria and informed consent. After conditioning with Fludarabine and Cyclophosphamide, patients will receive a single infusion of BCMA CAR NK cells with close monitoring using one of the following dose levels: * Dose Level 1: 1×10\^7/Kg * Dose Level 2: 5×10\^7/Kg * Dose Level 3: 1×10\^8/Kg Safety Assessment: Adverse events will be recorded and graded. Laboratory parameters and cytokine release syndrome (CRS) markers will be closely monitored. Efficacy Evaluation: Response assessments will follow IMWG guidelines, including complete response (CR), partial response (PR), stable disease (SD), and progressive disease.
Sponsors
Shahid Beheshti University of Medical Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age 18-80 years with expected survival \> 3 months. 2. Confirmed diagnosis of active multiple myeloma with detectable BCMA expression in malignant cells. 3. Relapsed or refractory disease with at least 2 prior lines of treatment, including a proteasome inhibitor and immunomodulator, without achieving significant efficacy. 4. Measurable disease at screening according to IMWG criteria, as defined by any of the following: Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level being as defined； or light chain MM without measurable disease in the serum or the urine； serum immunoglobulin free light chain disease dL and abnormal serum immunoglobulin kappa/lambda free light chain ratio 5. ECOG performance status of 0-1. 6. Acceptable cardiac, liver, and kidney function. 7. Signed written informed consent.
Exclusion criteria
1. Pregnant or lactating women. 2. Uncontrolled active infection, HIV infection, or positive syphilis serology reaction. 3. Active hepatitis B or hepatitis C infection. 4. Recent or current use of glucocorticoids or other immunosuppressors. 5. Severe cardiac, liver, renal insufficiency, diabetes, or other diseases. 6. Participation in other clinical research in the past three months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of dose-limiting toxicity (DLTs) | 4 weeks | Incidence of dose-limiting toxicity (DLTs) within 4 weeks after infusion, characterized by \>= Grade 3 signs/symptoms according to CTCAE v4.03, to assess safety and tolerability. |
| Assessment of Maximum Tolerated Dose (MTD) | 4 weeks | — |
| Overall Remission Rate (ORR) | 8 weeks | Overall Remission Rate (ORR) two months after infusion, assessed using International Myeloma Working Group (IMWG) criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | 48 weeks | Progression-free survival (PFS) for up to 12 months, assessed using IMWG criteria. |
| Duration of Response (DOR) | 48 weeks | Duration of Response (DOR) for up to 12 months, assessed using IMWG criteria. |
Countries
Iran
Outcome results
None listed