Anti-BCMA CAR-NK Therapy in Relapsed or Refractory Multiple Myeloma

NCT ID: NCT06242249

Last Updated: 2024-03-06

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-30
• Study Completion Date: 2026-06-30

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.

Conditions

Multiple Myeloma, Refractory

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Relapsed or Refractory Multiple Myeloma

Group Type: EXPERIMENTAL

Anti-BCMA CAR-NK

Intervention Type: BIOLOGICAL

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.

Interventions

Anti-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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Shahid Beheshti University of Medical Sciences

OTHER

Sponsor Role: lead

Responsible Party

Masoud Soleimani

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Shariati Hospital

Tehran, , Iran

Countries

Iran

Facility Contacts

Masoud Soleimani, Prof.

Role: primary

Other Identifiers

74932

Identifier Type: -

Identifier Source: org_study_id