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| ID | Type | Description | Link |
|---|---|---|---|
| Nanjing Reindeer Biotechnology | Other Grant/Funding Number | Nanjing Reindeer Biotechnology Co., Ltd. |
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This study is a single-center, open-label, dose-exploration trial designed to evaluate the tolerability and safety of different doses of IASO104 in patients with relapsed/refractory plasma cell neoplasms, determine the recommended dose of IASO104, and assess its pharmacokinetic and pharmacodynamic characteristics. Additionally, the study will preliminarily observe the efficacy of the investigational drug in a small sample of subjects with relapsed/refractory multiple myeloma.
This study adopts a "3+3" dose-escalation design, with three predefined dose levels: 0.5×10⁶ CAR-T cells/kg, 1.0×10⁶ CAR-T cells/kg, and 3.0×10⁶ CAR-T cells/kg, administered as a single infusion.For each dose group, the first subject must be observed for at least 2 weeks after infusion before subsequent subjects can be treated. If stable biological activity or clinical benefit is observed at a lower dose level, the study may proceed with 1-2 expanded dose groups at lower levels after discussion between the investigator and sponsor, without requiring MTD determination.During the dose-escalation phase, 2-3 subjects will be enrolled per dose level, with the total number of subjects depending on the escalation progression (estimated 4-6 subjects in this phase). Treatment in the next dose group may only begin after all subjects in the current group have completed DLT assessment post-infusion.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| IASO104 | Experimental | IASO104 will be administered in one infusion. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IASO104 | Biological | IASO104 is a personalized, BCMA-targeted, genetically modified autologous T-cell immunotherapy product. |
|
| Measure | Description | Time Frame |
|---|---|---|
| incidence and severity of adverse events (AEs) | Minimum 2 years after IASO104 infusion |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Response Rate (ORR) | The proportion of subjects achieving stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) after treatment with IASO104 injection | Minimum 2 years after IASO104 infusion |
| Duration of Response (DOR) |
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Inclusion Criteria:
Age 18-75 years, any gender.
Diagnosis of multiple myeloma (MM) per International Myeloma Working Group (IMWG) diagnostic criteria.
Prior therapy requirements:
MM patients: ≥3 prior lines of therapy, including:
Primary plasma cell leukemia (pPCL): ≥1 prior line including ≥1 PI and ≥1 IMiD.
Documented disease progression during/within 12 months after last anti-myeloma therapy (exemption: No 12-month requirement if last line was CAR-T).
Measurable disease at screening (≥1 of the following):
Serum M-protein:
IgG ≥10 g/L IgA/IgD/IgE/IgM ≥5 g/L Urine M-protein ≥200 mg/24h Serum free light chains (FLC): Involved FLC ≥100 mg/L with abnormal κ/λ ratio Bone marrow plasma cells ≥30% (if no measurable M-protein/FLC).
ECOG performance status 0-1.
Life expectancy ≥12 weeks.
Adequate organ function (all lab values within 7 days prior to enrollment):
Hematology:
Absolute neutrophil count (ANC) ≥1×10⁹/L (allowed: growth factor support, but none within 7 days) Absolute lymphocyte count (ALC) ≥0.3×10⁹/L Platelets ≥50×10⁹/L (no transfusion within 7 days) Hemoglobin ≥60 g/L (no RBC transfusion within 7 days; erythropoietin allowed)
Liver:
ALT/AST ≤2.5×ULN Total bilirubin ≤1.5×ULN Renal: Calculated CrCl ≥40 mL/min (Cockcroft-Gault)
Coagulation:
Fibrinogen ≥1.0 g/L aPTT/PT ≤1.5×ULN Pulmonary: SpO₂ >91% (room air) Cardiac: LVEF ≥50% (echocardiography).
Contraception: Subjects/partners must use effective contraception from consent through 1 year post CAR-T infusion (excluded: calendar method).
Signed informed consent approved by the Ethics Committee prior to screening.
Exclusion Criteria:
Active graft-versus-host disease (GVHD) or requiring long-term immunosuppressive therapy.
Prior hematopoietic stem cell transplantation (HSCT):
Autologous HSCT (Auto-HSCT) within 12 weeks before apheresis,
≥2 prior Auto-HSCTs, Any prior allogeneic HSCT (Allo-HSCT).
Prior cell therapy targeting plasma cells within 3 months before apheresis, or detectable residual cellular therapy products in peripheral blood.
Recent anti-myeloma therapies (relative to apheresis):
Monoclonal antibody treatment within 21 days, Cytotoxic chemotherapy or proteasome inhibitors within 14 days, Immunomodulatory drugs within 7 days, Other anti-tumor therapies within 14 days or 5 half-lives (whichever is shorter).
Chronic corticosteroid use (>20 mg/day prednisone or equivalent), except for physiologic replacement, topical, or inhaled use.
Uncontrolled hypertension despite medication.
Severe cardiac disease, including:
Unstable angina, Myocardial infarction (within 6 months before screening), Congestive heart failure (NYHA Class ≥III), Severe arrhythmias.
Unstable systemic illnesses per investigator's judgment (e.g., severe hepatic, renal, or metabolic disorders requiring medication).
Other malignancies within 5 years, excluding:
Carcinoma in situ of the cervix, Basal/squamous cell skin cancer, Localized prostate cancer post-radical resection, Ductal breast carcinoma in situ post-resection.
History of solid organ transplantation.
Suspected or confirmed CNS involvement by plasma cell neoplasms.
Major surgery within 2 weeks before apheresis or planned within 2 weeks post-treatment (allowed: minor procedures under local anesthesia).
Investigational drugs within 1 month before apheresis.
Uncontrolled active infections:
Persistent symptoms despite appropriate therapy, Requiring IV antimicrobials at screening.
Viral infections:
HBV: HBsAg(+) or HBcAb(+) with detectable HBV DNA, HCV: HCV Ab(+) with detectable HCV RNA, HIV Ab(+), CMV DNA(+), Syphilis: TRUST(+) and TPPA(+).
Pregnancy or lactation.
Psychiatric disorders, cognitive impairment, or active CNS diseases.
Other conditions deemed ineligible by the investigator.
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| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| D007952 | Leukemia, Plasma Cell |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
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Duration of response (DOR) was defined as the time from the first documented achievement of response (≥ partial response [PR]) to disease progression or death from any cause (whichever occurred first) in subjects treated with IASO104 injection. |
| Minimum 2 years after IASO104 infusion |
| Progression-Free Survival (PFS) | Progression-free survival (PFS) was defined as the time from initiation of IASO104 injection treatment to disease progression or death from any cause, whichever occurred first. | Minimum 2 years after IASO104 infusion |
| Overall Survival (OS) | Overall survival (OS) was defined as the time from initiation of IASO104 injection treatment to death from any cause. | Minimum 2 years after IASO104 infusion |
| Time to Response (TTR) | Time to response (TTR) was defined as the interval from initiation of IASO104 injection treatment to first achievement of disease response (≥ partial response [PR]). | Minimum 2 years after IASO104 infusion |
| Time to Complete Response (TTCR) | Time to complete response (TTCR) was defined as the interval from initiation of IASO104 injection treatment to first achievement of complete response (CR) or better (including stringent complete response [sCR]) | Minimum 2 years after IASO104 infusion |
| Minimal Residual Disease (MRD)-negative rate | Proportion of subjects achieving bone marrow minimal residual disease (MRD)-negativity by next-generation flow cytometry (NGF) following study treatment | Minimum 2 years after IASO104 infusion |
| Duration of MRD Negativity | Duration of MRD negativity was defined as the time from first achievement of MRD-negative status to first MRD recurrence (conversion to positive) | Minimum 2 years after IASO104 infusion |
| Pharmacokinetic (PK) Endpoints | Peak concentration (C<sub>max</sub>) of CAR-T cells Area under the curve (AUC) over: 0-28 days post-infusion (AUC<sub>0-28d</sub>) 0-90 days post-infusion (AUC<sub>0-90d</sub>) 0-180 days post-infusion (AUC<sub>0-180d</sub>) Infusion to last measurable timepoint (AUC<sub>0-last</sub>) | Minimum 2 years after IASO104 infusion |
| Pharmacokinetic (PK) Endpoints | vector copy number (VCN) in peripheral blood Time to peak concentration (T<sub>max</sub>) Area under the curve (AUC) over: 0-28 days post-infusion (AUC<sub>0-28d</sub>) 0-90 days post-infusion (AUC<sub>0-90d</sub>) 0-180 days post-infusion (AUC<sub>0-180d</sub>) Infusion to last measurable timepoint (AUC<sub>0-last</sub>) | Minimum 2 years after IASO104 infusion |
| Pharmacodynamic (PD) Endpoints | Levels of soluble BCMA (sBCMA) in peripheral blood at each timepoint | Minimum 2 years after IASO104 infusion |
| Pharmacodynamic (PD) Endpoints | concentrations of CAR-T-related inflammatory biomarkers (including CRP, IL-6, and ferritin) | Minimum 2 years after IASO104 infusion |
| D014652 |
| Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D007938 | Leukemia |