Multiple myeloma
Conditions
Interventions
Low dose experimental group:The dual-targeting BCMA and GPRC5D chimeric antigen receptor T (CAR-T) cell product SKLB-BiCAR01, 1×10^6 CAR T cells/Kg
Medium dose experimental group:The dual-targeting BCMA and GPRC5D chimeric antigen receptor T (CAR-T) cell product SKLB-BiCAR01, 3×10^6 CAR T cells/Kg
High dose experimental group:The dual-targeting BCMA and GPRC5D chimeric antigen receptor T (CAR-T) cell product SKLB-BiCAR01, 6×10^6 CAR T cells/Kg
Dose expansion group:The dual-targeting BCMA and GPRC5D chimeric antigen receptor T (CAR-T) cell product SKLB-BiCAR01, with the treatment dose being determined based on the established MTD, RP2D, and/
Sponsors
Dapartment of Hematology, West China Hospital, Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. Male or female participants aged 18 to 70 years at the time of signing informed consent 2. Confirmed diagnosis of Multiple Myeloma according to the IMWG criteria 3. The presence of a measurable disease at the time of screening, determined by at least one of the criteria: (1). Serum M protein >= 10 g/L for IgG-type MM or >= 5 g/L for IgA, IgD, IgE, or IgM MM; or (2). Urine Protein M level >= 200 mg/24 hours; or (3). Light chain MM with serum free light chain (sFLC) >= 100 mg/L and abnormal k/? FLC ratio; or (4). Presence of extramedullary lesions. 4. Bone marrow plasma cells or bone marrow tissue measuring BCMA expression =50%; bone marrow plasma cells GPRC5D expression =20%; and the expression of target antigens can be detected by immunohistochemistry or flow cytometry of tumor tissue 5. Have received at least 3 lines of prior therapy for multiple myeloma and undergone at least 1 complete cycle of treatment for each regimen, unless the best response to the regimen best remission status was PD (according to IMWG criteria) 6. Prior lines of therapy should include one PI and one IMiD 7. During the most recent treatment process or within 12 months afterward, there must be evidence of disease progression based on efficacy assessments according to the IMWG criteria referenced by the investigator. Disease non-response is defined as the failure to achieve at least a minimal response or the occurrence of disease progression (PD) during treatment. Additionally, participants with evidence of disease progression (as described above) in the past 6 months, who subsequently demonstrated refractory disease or lack of response in the most recent first-line treatment, may be eligible for inclusion in the study 8. ECOG performance status class of 0 or 1 9. Expected survival >= 12 weeks 10. Screening clinical laboratory values meet the following criteria (1) Complete Blood Count 1)Hemoglobin >= 8.0 g/dL (no red blood cell [RBC] transfusions within 7 days prior to the laboratory test; recombinant human erythropoietin is permitted)* 2) Platelets >= 50 x 10^9/L (must not have received transfusion support within 7 days prior to laboratory test) 3) Lymphocyte count >= 0.3×10^9/L 4) Absolute neutrophil count (ANC) >=0.75×10^9/L (allows the use of growth factor supportive treatment, but must not have received supportive treatment within 7 days prior to laboratory testing) (2)Biochemistry: 1) AST and ALT =40 mL/min/1.73 m^2 , based on the Modified Dietary Formula for Kidney Disease (or 24-hour urine collection) 3) Total bilirubin = 8.0 g/dL are permitted after the first hematology test at Screening for subjects who meet the inclusion criteria at Screening 11. Females of childbearing potential must have a negative high-sensitivity serum pregnancy test (ß-human chorionic gonadotropin [ß-hCG]) at Screening and prior to first treatment with cyclophosphamide and fludarabine 12. Men of childbearing potential, ensure that sexual partners are effectively contracepting; women of childbearing potential, use effective contraception and agree to use such contraception throughout the study period. See the Annex to this protocol for details on contraceptive measures, definition of women of childbearing potential, and contraceptiv
Exclusion criteria
Exclusion criteria: 1. Diagnosed with or treated for other invasive malignancies besides multiple myeloma, with the following exceptions: (1) Malignant tumors that have received curative treatment and show no known active disease for >=2 years prior to enrollment, or (2) Adequately treated non-melanoma skin cancer, with no evidence of disease 2. Previously received the following anti-tumor therapies (before apheresis): (1) Targeted therapy, epigenetic therapy, or experimental drug therapy, or used invasive experimental medical devices within 14 days or at least five half-lives (whichever is shorter); (2) Monoclonal antibody therapy for multiple myeloma within 21 days; (3) Cytotoxic therapy within 14 days; (4) Proteasome inhibitor treatment within 14 days; (5) Immunomodulatory therapy within 7 days; (6) Radiation therapy within 14 days. However, if the radiation field covers =5% of bone marrow reserves, the subject is eligible for the study regardless of the radiation end date 3. Apart from hair loss or peripheral neuropathy, toxicities from previous anti-tumor treatments must have returned to baseline levels or =470 milliseconds; (7) Uncontrolled hypertension (systolic BP >=150 mmHg and/or diastolic BP >=95 mmHg) 5. Cumulative use of corticosteroids equivalent to =70 mg of prednisone within 7 days before apheresis 6. Previous receipt of any of the following treatments (1) Allogeneic stem cell transplant for multiple myeloma; (2) Autologous stem cell transplant =12 weeks before apheresis 7. Known active central nervous system (CNS) involvement or a history of CNS involvement, or clinical signs of leptomeningeal/meningeal involvement from multiple myeloma 8. Stroke or seizure occurring within 6 months prior to signing the informed consent form (ICF) 9. At screening, diagnosed with plasma cell leukemia (according to standard classification, plasma cells >2.0×10^9/L), Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or primary AL amyloidosis 10. HIV seropositive 11. Received a live attenuated vaccine within 4 weeks before apheresis 12. Hepatitis B infection as defined by the appendix. If infection status is unclear, quantitative hepatitis B virus DNA levels must be used to determine infection status 13. Hepatitis C infection (defined as positive anti-hepatitis C virus [HCV] antibodies and positive HCV-RNA quantitative test results) or a known history of hepatitis C. For subjects who have recovered from a previous infection and show positive HCV antibodies, they can only be enrolled if a confirmatory HCV RNA test result is undetectable. For subjects with a history of HCV infection, sustained virological response (SVR, defined as >=24 weeks after completion of antiviral therapy) must be confirmed to determine eligibility 14. Requiring oxygen supplementation to maintain adequate blood oxy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum Tolerated Dose, MTD;Recommended Phase II Dose;The frequency and severity grading of Adverse Events (AEs) and Serious Adverse Events (SAEs) ; | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall Response Rate (ORR), the percentage of patients who achieve a partial response (PR) or better in accordance with the International Myeloma Working Group (IMWG) criteria;Duration of Response (DOR) and Time to Response (TTR) ;Progression-Free Survival, PFS;Overall Survival, OS; | — |
Countries
China
Contacts
Public ContactTing Niu
West China Hospital, Sichuan University
Outcome results
None listed