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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Multiple Myeloma, Refractory
• Intervention / Treatment: Biological: Anti-BCMA CAR-NK

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of
    • Shariati Hospital
    • Contact: Masoud Soleimani, Prof.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Relapsed or Refractory Multiple Myeloma

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	Progression-free survival (PFS) for up to 12 months, assessed using IMWG criteria.	48 weeks
Duration of Response (DOR)	Duration of Response (DOR) for up to 12 months, assessed using IMWG criteria.	48 weeks

Collaborators and Investigators

• Sponsor: Shahid Beheshti University of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Estimated): April 30, 2024
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: January 27, 2024
• First Submitted That Met QC Criteria: January 27, 2024
• First Posted (Actual): February 5, 2024

Study Record Updates

• Last Update Posted (Actual): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 3, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: CAR-NK Therapy; Anti-BCMA
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: 74932

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No