Evaluating a new CAR-NK cell treatment for relapsed multiple myeloma and plasma cell leukemia

A Early Phase 1 Clinical Trial to Evaluate the Safety and Efficacy of Human BCMA Targeted CAR-NK Cells Injection for Subjects With Relapsed/Refractory Multiple Myeloma or Plasma Cell Leukemia

This study is testing a new CAR-NK cell treatment to see if it can help people with relapsed multiple myeloma or plasma cell leukemia feel better and improve their condition.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hrain Biotechnology Co., Ltd. (Industry-sponsored)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06045091 on ClinicalTrials.gov

What this trial studies

This is a single-arm, open-label, dose-escalation trial aimed at assessing the safety, tolerability, and pharmacokinetic/pharmacodynamic characteristics of human BCMA targeted CAR-NK cell injections in patients with relapsed or refractory multiple myeloma or plasma cell leukemia. Eligible participants will undergo preconditioning chemotherapy before receiving the CAR-NK cell infusion, followed by monitoring for adverse events and efficacy outcomes. Comprehensive eligibility assessments will be conducted, including physical exams and imaging tests, to ensure participant safety and suitability for the trial.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with documented relapsed or refractory multiple myeloma or plasma cell leukemia who meet specific eligibility criteria.

Not a fit: Patients with early-stage multiple myeloma or those who are not relapsed or refractory may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat relapsed or refractory multiple myeloma and plasma cell leukemia.

How similar studies have performed: While CAR-T cell therapies have shown promise in similar conditions, this specific approach using CAR-NK cells is relatively novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:Subjects must meet all of the following criteria to be enrolled:

* Subjects volunteer to participate in clinical trials, understand and sign the informed consent document, be willing to complete all the trial procedures;
* 18 years and older, Male and female;
* Expected survival \> 12 weeks;
* Documented evidence of multiple myeloma at diagnosis as defined by IMWG updated criteria (2014), or plasma cell leukemia at diagnosis as defined by Diagnosis and therapeutic criteria of hematologic disease (4th edition);
* One of the following indicators is satisfied:

  1. Serum M protein: IgG M protein ≥5 g/L; or IgA M protein ≥5 g/L; or IgD M protein and IgD \>ULN;
  2. Urine M protein ≥200 mg/24h;
  3. Affected serum free light chain ≥100 mg/L and Serum free light chain ratio is abnormal;
  4. Clonal bone marrow plasma cells ≥10 % for non-secretory myeloma;
* Patients with relapsed/refractory multiple myeloma or plasma cell leukemia, satisfying:

  1. Patients have received at least 3 prior MM or PCL treatment regimens containing at least one proteasome inhibitor and one immunomodulatory;
  2. Progress is documented within 60 days of the most recent anti-tumor treatment, or efficacy assessment does not reach minimal response(MR) or above;
* Liver, kidney and cardiopulmonary functions meet the following requirements:

  1. Creatinine clearance rate (estimated by CockcroftGault formula) ≥30mL/min;
  2. Left ventricular ejection fraction \> 50%;
  3. Baseline peripheral oxygen saturation \> 95%;
  4. Total bilirubin≤ 2×ULN; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×ULN;
* Blood routine examination satisfying hemoglobin≥60 g/L, neutrophils≥ 1.0×10\^9/L, and platelets≥30×10\^9/L, can complete this trial according to the judgement of investigators.

Exclusion Criteria:Any one of the following conditions cannot be selected as a subject：

* Accompanied by other uncontrolled malignancies;
* Subjects with positive Hepatitis B surface antigen(HBsAg) or Hepatitis B core antibody (HBcAb) and hepatitis B virus (HBV) DNA titers higher than the lower limit of the normal range of the investigative site; Hepatitis C virus (HCV) antibody positive and peripheral blood HCV RNA positive; Human Immunodeficiency Viral (HIV) antibody positive; syphilis primary screening antibody positive;
* Any instability of systemic disease, including but not limited to unstable angina, cerebrovascular accident, or transient cerebral ischemic (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), congestive heart failure (New York heart association (NYHA) classification ≥ III), need drug therapy of severe arrhythmia, liver, kidney, or metabolic disease;
* Subjects who are considered unsuitable to participate in this trial by the investigator.
* Pregnant or lactating woman, and female subject who plans to have a pregnancy within 1 year after cell transfusion, or male subject whose partner plans to have a pregnancy within 1 year after cell transfusion;
* Received CAR-NK treatment or other gene therapies before enrollment;
* Subjects who have a disease that affects the signing of written informed consent or who are unable to comply with research procedures; or who are unwilling or unable to comply with research requirements;
* Subjects who have had severe immediate hypersensitivity reactions to any drugs used in this research;
* Active or uncontrollable infection requiring systemic therapy within 14 days prior to enrollment;
* In the past two years, the terminal organ was damaged due to autoimmune diseases (such as Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus), or the systemic use of immunosuppressive or other systemic disease control drugs was required;
* Patients with symptoms of central nervous system.

Where this trial is running

Shanghai, Shanghai Municipality

• Shanghai Changzheng Hospital — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: Juan Du, Doctor — Shanghai Changzheng Hospital
• Study coordinator: Xuedong Sun, Doctor

Conditions Multiple Myeloma; Plasma Cell Leukemia; BCMA; CAR-NK; Relapsed /Refractory