SL4903 CAR-T Therapy for Relapsed/Refractory Multiple Myeloma

NCT ID: NCT07234721

Last Updated: 2026-02-10

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-02-01
• Study Completion Date: 2028-10-30

Brief Summary

This is a Phase I, single-center, single-arm, open-label clinical study to evaluate the safety, tolerability, and preliminary efficacy of SL4903 autologous T-cell injection (CAR-T cell therapy) in adult patients with relapsed or refractory multiple myeloma (r/r MM) who have failed prior standard therapies.

The study employs a "3+3" dose-escalation design with three planned dose levels (1×10⁶, 2×10⁶, and 3×10⁶ CAR+ cells/kg). Approximately 9 to 18 evaluable subjects will be enrolled to determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D), and to characterize the safety profile and potential anti-myeloma activity of SL4903.

Conditions

Relapsed and Refractory Multiple Myeloma (RRMM)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1: dosage 1×10⁶ CAR⁺ cells/kg

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).

Group Type: EXPERIMENTAL

SL4903 Autologous T-Cell Injection

Intervention Type: DRUG

Eligible subjects, identified through application of inclusion/exclusion criteria, will be evaluated for tumor type, tumor burden, vital-sign status, and other comprehensive factors before receiving SL4903(1×10⁶ CAR⁺ cells/kg) cellular therapy.

Arm 2: dosage 2×10⁶ CAR⁺ cells/kg

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).

Group Type: EXPERIMENTAL

SL4903 Autologous T-Cell Injection

Intervention Type: DRUG

Eligible subjects, identified through application of inclusion/exclusion criteria, will be evaluated for tumor type, tumor burden, vital-sign status, and other comprehensive factors before receiving SL4903(2×10⁶ CAR⁺ cells/kg) cellular therapy.

Arm 3: dosage 3×10⁶ CAR⁺ cells/kg

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).

Group Type: EXPERIMENTAL

SL4903 Autologous T-Cell Injection

Intervention Type: DRUG

Eligible subjects, identified through application of inclusion/exclusion criteria, will be evaluated for tumor type, tumor burden, vital-sign status, and other comprehensive factors before receiving SL4903(3×10⁶ CAR⁺ cells/kg) cellular therapy.

Interventions

SL4903 Autologous T-Cell Injection

Eligible subjects, identified through application of inclusion/exclusion criteria, will be evaluated for tumor type, tumor burden, vital-sign status, and other comprehensive factors before receiving SL4903(1×10⁶ CAR⁺ cells/kg) cellular therapy.

Intervention Type: DRUG

SL4903 Autologous T-Cell Injection

Eligible subjects, identified through application of inclusion/exclusion criteria, will be evaluated for tumor type, tumor burden, vital-sign status, and other comprehensive factors before receiving SL4903(2×10⁶ CAR⁺ cells/kg) cellular therapy.

Intervention Type: DRUG

SL4903 Autologous T-Cell Injection

Eligible subjects, identified through application of inclusion/exclusion criteria, will be evaluated for tumor type, tumor burden, vital-sign status, and other comprehensive factors before receiving SL4903(3×10⁶ CAR⁺ cells/kg) cellular therapy.

Intervention Type: DRUG

Eligibility 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 according to IMWG 2016 criteria, meeting the following conditions:

1. Patients must have received at least one prior line of anti-myeloma therapy, including treatment with proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and anti-CD38 monoclonal antibodies, or patients with multiple myeloma refractory to proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies;

2. Documented evidence of disease progression or failure to achieve complete response (CR) following the last line of therapy, as assessed by the investigator according to IMWG criteria.

4. Measurable disease at screening, defined as meeting one or more of the following criteria:

• 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
• Soft tissue extramedullary disease (EMD) identified by radiographic imaging with a longest diameter ≥ 2 cm

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: Hemoglobin ≥ 60 g/L, platelets ≥ 50 × 10⁹/L, and lymphocytes ≥ 0.3 × 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hebei Senlang Biotechnology Inc., Ltd.

INDUSTRY

Sponsor Role: collaborator

Institute of Hematology & Blood Diseases Hospital, China

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

An

Role: PRINCIPAL_INVESTIGATOR

Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences,Tianjin

Central Contacts

Gang An, PhD&MD

Role: CONTACT

angang@ihcams.ac.cn

86-022-23909171

Other Identifiers

IIT2025098

Identifier Type: -

Identifier Source: org_study_id