IL-15–armored CAR-T for relapsed or refractory multiple myeloma and plasma cell leukemia

A Clinical Study Evaluating the Safety and Efficacy of IL-15-armored Novel CAR-T Cell Therapy in Patients With Relapsed/Refractory Multiple Myeloma and Plasma Cell Leukemia

This trial will test IL-15–armored CAR-T cell therapy to see if it helps adults with relapsed or refractory multiple myeloma or plasma cell leukemia, including those with persistent or returning MRD.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: The First Hospital of Jilin University (Academic / other)
• Drugs / interventions: CAR-T, chimeric antigen receptor
• Locations: 1 site (Changchun, Jilin)
• Trial ID: NCT07509086 on ClinicalTrials.gov

What this trial studies

This open-label, single-arm Phase 2 trial uses autologous T cells engineered to express a chimeric antigen receptor plus IL-15 to enhance in vivo expansion and persistence. Participants undergo leukapheresis for CAR-T manufacturing, lymphodepleting conditioning, and a single CAR-T infusion; bridging therapy and localized radiotherapy are allowed per investigator discretion. Primary endpoints focus on efficacy and safety, while extensive exploratory correlative studies will use single-cell and bulk RNA sequencing, spatial transcriptomics, and serial ctDNA to characterize tumor microenvironment dynamics and predictors of response and toxicity. Subjects will be followed post-infusion for clinical outcomes and adverse events according to the protocol.

Who should consider this trial

Good fit: Adults 18–80 years with relapsed or refractory multiple myeloma or plasma cell leukemia, including those with persistent MRD positivity or conversion to MRD positivity, who meet organ-function and performance-status requirements.

Not a fit: Patients with severe organ dysfunction, life expectancy under three months, uncontrolled infection, or who cannot access the single study site are unlikely to benefit or qualify.

Why it matters

Potential benefit: If successful, this approach could produce deeper or more durable remissions by improving CAR-T expansion and persistence in heavily pretreated myeloma or PCL patients.

How similar studies have performed: BCMA-targeted CAR-T therapies have produced high response rates in relapsed myeloma, but IL-15–armored CAR-T is a newer modification with promising preclinical data and limited clinical experience so far.

Eligibility criteria

Inclusion Criteria:

1. Able and willing to provide written informed consent and comply with the scheduled visits, study treatment, laboratory assessments, and other study procedures.
2. Clinically diagnosed relapsed or refractory multiple myeloma or plasma cell leukemia (PCL). Patients with persistent minimal residual disease (MRD) positivity or conversion from MRD-negative to MRD-positive status following induction and consolidation therapy are also eligible for enrollment.
3. Age 18 to 80 years, inclusive.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-3.
5. Estimated life expectancy \> 3 months from the date of signing the informed consent form.
6. Hemoglobin ≥ 60 g/L (transfusion permitted).
7. Adequate organ function as defined below:

   * Creatinine clearance (CrCl) ≥ 40 mL/min, calculated using the Cockcroft-Gault formula;
   * Left ventricular ejection fraction (LVEF) ≥ 50%;
   * Oxygen saturation \> 90% on room air;
   * Total bilirubin ≤ 1.5 × upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN.
8. Participants of childbearing potential must agree to use effective contraception prior to study enrollment and for at least 6 months after completion of study treatment. Participants who become pregnant or suspect pregnancy must notify the investigator immediately.

Exclusion Criteria:

1. History within 1 year prior to signing the informed consent form of any of the following:

   * New York Heart Association (NYHA) Class III or IV heart failure;
   * Myocardial infarction;
   * Cardiac angioplasty or stent placement;
   * Unstable angina;
   * Other clinically significant symptomatic cardiac disease;
2. Active graft-versus-host disease (GVHD) or requirement for systemic immunosuppressive therapy.
3. History of other malignancies within 5 years prior to screening, except for adequately treated carcinoma in situ of the cervix, basal cell carcinoma or squamous cell carcinoma of the skin, localized prostate cancer after radical surgery, or ductal carcinoma in situ of the breast after curative surgery.
4. Active infection requiring systemic therapy or uncontrolled infection within 7 days prior to screening (excluding mild genitourinary or upper respiratory tract infections).
5. Evidence of active viral or infectious disease as follows:

   * Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with peripheral blood hepatitis B virus (HBV) DNA above the lower limit of detection;
   * Positive hepatitis C virus (HCV) antibody with detectable HCV RNA;
   * Positive human immunodeficiency virus (HIV) antibody;
   * Positive Treponema pallidum particle agglutination assay (TPPA).
6. Participation in another clinical trial within 4 weeks prior to signing the informed consent form, or if the time from the last dose of an investigational drug to informed consent is less than 5 half-lives of that drug (whichever is longer).
7. History of severe allergic reactions to biologic products.
8. Any unstable systemic disease, as judged by the investigator, including but not limited to severe hepatic, renal, or metabolic disorders requiring medical treatment.
9. Pregnant or breastfeeding women; women planning to become pregnant within 2 years after cell infusion; or male participants whose partners plan to become pregnant within 2 years after cell infusion.
10. Any condition that, in the opinion of the investigator, may increase the participant's risk or interfere with study participation or interpretation of study results.

Where this trial is running

Changchun, Jilin

• The First Hospital of Jilin University — Changchun, Jilin, China (Recruiting)

Conditions Relapsed/Refractory Multiple Myeloma; Plasma Cell Leukemia; IL-15-armored CAR-T