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

NCT06242249 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: 74932
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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

Keywords

CAR-NK Therapy; Anti-BCMA

Outcome Measures

Primary Outcomes (3)

• 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

• Assessment of Maximum Tolerated Dose (MTD)

  4 weeks

• Overall Remission Rate (ORR)

  Overall Remission Rate (ORR) two months after infusion, assessed using International Myeloma Working Group (IMWG) criteria.

  8 weeks

Secondary Outcomes (2)

• Progression-free survival (PFS)

  48 weeks

• Duration of Response (DOR)

  48 weeks

Study Arms (1)

Relapsed or Refractory Multiple Myeloma

EXPERIMENTAL

Biological: Anti-BCMA CAR-NK

Interventions

Anti-BCMA CAR-NK 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.

Relapsed or Refractory Multiple Myeloma

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-80 years with expected survival \> 3 months.
• Confirmed diagnosis of active multiple myeloma with detectable BCMA expression in malignant cells.
• Relapsed or refractory disease with at least 2 prior lines of treatment, including a proteasome inhibitor and immunomodulator, without achieving significant efficacy.
• 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
• ECOG performance status of 0-1.
• Acceptable cardiac, liver, and kidney function.
• Signed written informed consent.

You may not qualify if:

• Pregnant or lactating women.
• Uncontrolled active infection, HIV infection, or positive syphilis serology reaction.
• Active hepatitis B or hepatitis C infection.
• Recent or current use of glucocorticoids or other immunosuppressors.
• Severe cardiac, liver, renal insufficiency, diabetes, or other diseases.
• Participation in other clinical research in the past three months.

Sponsors & Collaborators

• Shahid Beheshti University of Medical Sciences: lead

Study Sites (1)

Shariati Hospital

Tehran, Iran

Location

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 27, 2024
• First Posted: February 5, 2024
• Study Start: April 30, 2024
• Primary Completion: April 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: March 6, 2024

Record last verified: 2024-03

Locations

IR (1)