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

Multiple Myeloma, Refractory Clinical Trial

Official title:

Determining Safety and Maximum Tolerated Dose (MTD) of Anti-BCMA CAR-NK Therapy in Relapsed or Refractory Multiple Myeloma

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06242249
• Other study ID #: 74932
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: April 30, 2024
• Est. completion date: June 30, 2026

Study information

• Verified date: March 2024
• Source: Shahid Beheshti University of Medical Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 10
• Est. completion date: June 30, 2026
• Est. primary completion date: April 30, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Multiple Myeloma, Refractory
• Neoplasms, Plasma Cell

Intervention

Biological:
• 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.

Locations

Country	Name	City	State
Iran, Islamic Republic of	Shariati Hospital	Tehran

Sponsors (1)

Lead Sponsor	Collaborator
Shahid Beheshti University of Medical Sciences

Country where clinical trial is conducted

Iran, Islamic Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose-limiting toxicity (DLTs)	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.	4 weeks
Primary	Assessment of Maximum Tolerated Dose (MTD)		4 weeks
Primary	Overall Remission Rate (ORR)	Overall Remission Rate (ORR) two months after infusion, assessed using International Myeloma Working Group (IMWG) criteria.	8 weeks
Secondary	Progression-free survival (PFS)	Progression-free survival (PFS) for up to 12 months, assessed using IMWG criteria.	48 weeks
Secondary	Duration of Response (DOR)	Duration of Response (DOR) for up to 12 months, assessed using IMWG criteria.	48 weeks