Clinical trial NCT06242249: Anti-BCMA CAR-NK Therapy in Relapsed or Refractory Multiple Myeloma
Official title: Determining Safety and Maximum Tolerated Dose (MTD) of Anti-BCMA CAR-NK Therapy in Relapsed or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma, Refractory
Keywords: CAR-NK Therapy
Anti-BCMA
Lead sponsor: Shahid Beheshti University of Medical Sciences
Sponsor class: OTHER
First posted: 2024-02-05
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Incidence of dose-limiting toxicity (DLTs)
timeFrame: 4 weeks
measure: Assessment of Maximum Tolerated Dose (MTD)
timeFrame: 4 weeks
measure: Overall Remission Rate (ORR)
timeFrame: 8 weeks
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: 48 weeks
measure: Duration of Response (DOR)
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Tehran
country: Iran, Islamic Republic of
facility: Shariati Hospital
Study officials:
References: