SL4903 CAR-T Therapy for r/r MM With Extramedullary Disease

Institute of Hematology & Blood Diseases Hospital, China

Status and phase: Not yet enrolling; Early Phase 1

Conditions: Extramedullary Disease in Multiple Myeloma

Treatments: Drug: SL4903 Autologous T-Cell Injection

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT07234721

IIT2025098

Details and patient eligibility

About

This study is a single-center, single-arm, open-label clinical trial designed to evaluate the safety and efficacy of SL4903 cell therapy in relapsed or refractory multiple myeloma patients with extramedullary disease.

After being screened by the inclusion/exclusion criteria, eligible subjects were administered SL4903 cell therapy.

This study follows the "3+3" dose escalation model, with three dose cohorts (1×10^6, 2×10^6, and 3×10^6 CAR+ cells/kg). A total of 9 to 18 subjects are expected to be enrolled to evaluate the safety and tolerability of SL4903 autologous T-cell injection and determine the maximum tolerated dose (MTD).

Enrollment: 9 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

Subjects must meet ALL of the following conditions:

1. Age 18-75 years; either sex.

2. Able to understand the study and provide voluntary written informed consent.

3. Histologically and/or cytologically confirmed multiple myeloma per IMWG 2016 criteria, AND all of the following:

   1. Received at least two prior lines of anti-myeloma therapy, including prior exposure to (or refractoriness/intolerance of) a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.
   2. Progressive disease or failure to achieve response after the most recent therapy, as judged by the investigator using IMWG criteria.
   3. Extramedullary disease on imaging: at least one para-osseous lesion >5 cm or non-para-osseous lesion >2 cm.

4. Measurable disease at screening, defined by any one or more of:

   • Serum M-protein ≥0.5 g/dL
   • Urinary M-protein ≥200 mg/24 h
   • Abnormal serum FLC ratio (<0.26 or >1.65) with involved FLC ≥10 mg/dL

5. ECOG performance status 0-2.

6. Adequate organ function:

   1. Serum creatinine ≤150 µmol/L or calculated creatinine clearance (Cockcroft-Gault) ≥40 mL/min (may be relaxed for acute MM-related renal impairment at investigator discretion).
   2. Total bilirubin ≤2×ULN; ALT ≤3×ULN; AST ≤3×ULN.
   3. Normal diastolic function on echocardiography, LVEF ≥50 %, no significant arrhythmia.
   4. No active pulmonary infection; oxygen saturation on room air >90 %.

7. No contraindication to leukapheresis: Hb ≥60 g/L, platelets ≥50×10⁹/L, ANC ≥1×10⁹/L.

8. Life expectancy >12 weeks.

9. Women of child-bearing potential must have a negative urine pregnancy test and must not be breastfeeding; all men and women with reproductive potential must use effective contraception throughout the study.

Exclusion Criteria

A subject will be excluded if ANY of the following apply:

1. History of severe immediate hypersensitivity to any study drug.

2. Central nervous system (CNS) disorders such as epilepsy, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, or neuropathy (resolved cases without residual symptoms may be exempted at the investigator's discretion). Active CNS involvement, prior CNS myelomatous disease, or meningeal/spinal cord involvement signs must be excluded.

3. Prior traumatic brain injury, cerebrovascular accident, significant cerebral ischemia, or intracranial hemorrhage.

4. Concurrent uncontrolled malignancies other than adequately treated cervical carcinoma in situ, basal-cell or squamous-cell skin carcinoma, localized prostate cancer after radical surgery, ductal carcinoma in situ after radical surgery, or thyroid cancer after curative surgery.

5. Clinically significant cardiovascular disease, e.g., uncontrolled or symptomatic arrhythmia, congestive heart failure, or NYHA class III/IV cardiac disease; myocardial infarction, coronary angioplasty/stenting, unstable angina, or other clinically relevant cardiac disorders within 12 months before enrollment.

6. Any severe comorbidity or condition judged by the investigator to increase subject risk or interfere with the study, including but not limited to liver cirrhosis or recent major trauma.

7. Prior BCMA- and/or GPRC5D-directed CAR-T therapy.

8. Allogeneic hematopoietic stem-cell transplantation within 6 months before screening, or any immunosuppressive therapy for graft-versus-host disease during screening.

9. Autoimmune disease, immunodeficiency, or need for immunosuppressants (except low-dose corticosteroids).

10. Uncontrolled active infection, including but not limited to active tuberculosis; suspected or proven uncontrolled fungal, bacterial, viral, or other infections.

11. Live attenuated vaccine within 4 weeks before leukapheresis.

12. Active hepatitis (HBV-DNA or HCV-RNA above the lower limit of detection), syphilis infection, congenital or acquired immunodeficiency including HIV, EBV or CMV viremia (DNA above the lower limit of detection).

13. History of alcohol abuse, drug abuse, or psychiatric illness.

14. Inability to meet the following washout requirements prior to PBMC collection:

    1. Corticosteroids: no more than 5 mg prednisone (or equivalent) within 72 h.
    2. Anti-tumor therapies: targeted therapy, epigenetic therapy, investigational drugs/devices-discontinued ≥14 days or ≥5 half-lives (whichever is longer); anti-myeloma monoclonal antibodies-≥21 days; cytotoxic therapy-≥14 days; proteasome inhibitors-≥14 days; immunomodulatory drugs-≥7 days.
    3. Radiotherapy: completed ≥4 weeks before leukapheresis, except if the radiation field covers ≤5 % of marrow reserves.
    4. Anti-T-cell antibodies (e.g., alemtuzumab): discontinued ≥8 weeks.

15. Any condition judged by the investigator to render the subject unsuitable for enrollment.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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9 participants in 3 patient groups

Arm 1: dosage 1×10⁶ CAR⁺ cells/kg

Experimental group

Description:

In this dosage cohort (1×10⁶ CAR⁺ cells/kg). A total of 3-6 subjects are expected to be enrolled to evaluate the safety and tolerability of SL4903 autologous T-cell injection and to determine the maximum tolerated dose (MTD). Dose-Escalation Rules • In the "3 + 3" phase, one subject is enrolled into each dose level and observed for 28 days after cell infusion (the observation period may be prolonged at the investigator's discretion).

Treatment:

Drug: SL4903 Autologous T-Cell Injection

Drug: SL4903 Autologous T-Cell Injection

Drug: SL4903 Autologous T-Cell Injection

Arm 2: dosage 2×10⁶ CAR⁺ cells/kg

Experimental group

Description:

In this dosage cohort (2×10⁶ CAR⁺ cells/kg). A total of 3-6 subjects are expected to be enrolled to evaluate the safety and tolerability of SL4903 autologous T-cell injection and to determine the maximum tolerated dose (MTD). Dose-Escalation Rules • In the "3 + 3" phase, one subject is enrolled into each dose level and observed for 28 days after cell infusion (the observation period may be prolonged at the investigator's discretion).

Treatment:

Drug: SL4903 Autologous T-Cell Injection

Drug: SL4903 Autologous T-Cell Injection

Drug: SL4903 Autologous T-Cell Injection

Arm 3: dosage 3×10⁶ CAR⁺ cells/kg

Experimental group

Description:

In this dosage cohort (3×10⁶ CAR⁺ cells/kg). A total of 3-6 subjects are expected to be enrolled to evaluate the safety and tolerability of SL4903 autologous T-cell injection and to determine the maximum tolerated dose (MTD). Dose-Escalation Rules • In the "3 + 3" phase, one subject is enrolled into each dose level and observed for 28 days after cell infusion (the observation period may be prolonged at the investigator's discretion).

Treatment:

Drug: SL4903 Autologous T-Cell Injection

Drug: SL4903 Autologous T-Cell Injection

Drug: SL4903 Autologous T-Cell Injection