IL-15-Armored CAR-T Therapy in 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 is an open-label, single-arm, Phase 2 study to evaluate the efficacy and safety of IL-15-armored chimeric antigen receptor T-cell (CAR-T) therapy in subjects with relapsed or refractory multiple myeloma and plasma cell leukemia.

Study Overview

• Status: Recruiting
• Conditions: Relapsed/Refractory Multiple Myeloma; Plasma Cell Leukemia (PCL)
• Intervention / Treatment: Biological: IL-15-armored CAR-T cells

Detailed Description

This is an open-label, single-arm, Phase 2 study to evaluate the efficacy and safety of IL-15-armored CAR-T therapy in subjects with relapsed or refractory (R/R) multiple myeloma (MM) and plasma cell leukemia (PCL). Subjects with persistent measurable residual disease (MRD) positivity or conversion from MRD-negative to MRD-positive status are also eligible.

IL-15-armored CAR-T cells are autologous T lymphocytes genetically engineered to express a chimeric antigen receptor along with IL-15. The co-expression of IL-15 is intended to enhance in vivo expansion, persistence, and anti-tumor activity.

Subjects will undergo leukapheresis for CAR-T cell manufacturing, followed by lymphodepletion prior to infusion. Bridging therapy is permitted at the investigator's discretion, and radiotherapy is allowed before infusion for subjects with extramedullary disease.

After infusion, the efficacy and safety will be evaluated by the investigators.

Exploratory Objectives and Correlative Studies:

In addition to the primary efficacy and safety evaluations, exploratory analyses will be conducted to investigate clinical, biological, and treatment-related factors associated with treatment response and severe toxicity, with the aim of developing predictive models.

Multi-omics approaches, including single-cell sequencing, bulk RNA sequencing, and spatial transcriptomics, will be employed to characterize the dynamics of the tumor microenvironment.

Circulating tumor DNA (ctDNA) will be longitudinally collected from baseline through post-infusion follow-up. The associations between ctDNA dynamics and clinical outcomes will be assessed.

The clinical efficacy and biological mechanisms of radiotherapy (including site-directed radiotherapy and low-dose intestinal irradiation) in combination with CAR-T cell therapy will also be explored.

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Jilin
    • Changchun, Jilin, China, 130000
      • Recruiting
      • The First Hospital of Jilin University
      • Contact: FengYan Jin, MD, PhD; Phone Number: +8617843082307; Email: fengyanjin@jlu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

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: IL-15 armored CAR-T cells; Bridging therapy is permitted at the investigator's discretion. Radiotherapy is permitted before infusion for subjects with extramedullary disease. Lymphodepletion with fludarabine plus cyclophosphamide will be performed prior to CAR-T cells infusion.	Biological: IL-15-armored CAR-T cells; BCMA-targeted: 1.0/1.5/2.0 × 10^6 CAR-T cells; CD19/BCMA dual-targeted: 1.0/1.5/2.0 × 10^6 CAR-T cells; GPRC5D-targeted: 1.0/2.0/3.0 × 10^6 CAR-T cells.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	Percentage of participants with presence of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). ORR assessment will be based on International Myeloma Working Group (IMWG) response criteria.	From infusion to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response Rate	Percentage of participants who achieved CR or sCR according to IMWG Uniform Response Criteria for Multiple Myeloma	From infusion to 12 months
MRD-negative rate	Achieving measurable residual disease (MRD) negativity, as determined by multiparameter flow cytometry (MFC) or next-generation sequencing (NGS) after CAR-T cells infusion.	From infusion to 12 months
CR/MRD-negative rate	Percentage of participants who achieved both CR and MRD negativity with a sensitivity of 10^-4 or better within 12 months post infusion.	From infusion to 12 months
Time to Response	Time from infusion to first documentation of response of PR or better.	From infusion to 12 months
Duration of Response (DOR)	Time from first documentation of PR or better to first documentation of disease progression or death from any cause, whichever occurs first.	From first documentation of response through the end of follow-up (up to 24 months)
Progression-free survival (PFS)	Time from first infusion to first documentation of progressive disease (PD), or death due to any cause, whichever occurs first.	From infusion through the end of follow-up (up to 24 months)
Overall Survival (OS)	Time from first infusion to time of death due to any cause.	From infusion through the end of follow-up (up to 24 months)
Cmax	The maximum transgene level at Tmax.	From infusion to 12 months
Tmax	The time of maximum observed transgene level, obtained directly from the observed transgene level-time.	From infusion to 12 months
AUC (0-180 days)	The area under the curve (AUC) of the transgene level from the time of dosing to Day 180.	at Day 180 post infusion
Number of Participants With Safety Related Events	Number of participants with adverse events (AEs), adverse events of special interest (AESI), serious adverse events (SAEs), cytokine release syndrome, neurotoxicity, infection, and clinically significant laboratory abnormalities.	From enrollment through the end of follow-up (up to 24 months)

Collaborators and Investigators

• Sponsor: The First Hospital of Jilin University

Study record dates

Study Major Dates

• Study Start (Actual): December 29, 2025
• Primary Completion (Estimated): July 15, 2028
• Study Completion (Estimated): July 15, 2029

Study Registration Dates

• First Submitted: February 21, 2026
• First Submitted That Met QC Criteria: March 28, 2026
• First Posted (Actual): April 3, 2026

Study Record Updates

• Last Update Posted (Actual): April 3, 2026
• Last Update Submitted That Met QC Criteria: March 28, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Relapsed/Refractory Multiple Myeloma; Plasma Cell Leukemia; IL-15-armored CAR-T
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Leukemia; Hemic and Lymphatic Diseases; Multiple Myeloma; Leukemia, Plasma Cell
• Other Study ID Numbers: MM IL-15-Armored CAR-T

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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