Multiple myeloma
Conditions
Interventions
Case series:GB3007 NY-ESO1 TCRT injection
Sponsors
Zhongshan Hospital Affiliated to Fudan University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Male or female, aged 18-75 years; 2. Patients diagnosed as active myeloma at the initial diagnosis according to the Chinese guidelines for the diagnosis and treatment of multiple myeloma (2020 Edition); 3. Patients with the following HLA-A alleles: a0201, a0203, a0206; at the same time, patients with relapsed refractory MM with positive mRNA detection of bone marrow / pathological tissue, or positive ny-eso1 staining in bone marrow biopsy of patients with more than 25% staining by immunohistochemistry; 4. Refractory / recurrent was defined as: (1) Any treatment has never achieved minimal remission or more; (2) No response to salvage treatment or progression within 60 days after the last treatment; (3) For the definition of clinical recurrence, refer to the Chinese guidelines for the diagnosis and treatment of multiple myeloma, revised in 2020, and meet at least one of the following items: New bone lesions (proportion of bone marrow monoclonal plasma cells >=10%) or soft tissue plasmacytoma (except osteoporotic fracture) appeared; There was a definite increase in the number of existing plasmacytoma or bone lesions (the measured SPD increased by 50% and the absolute value >=1cm); Hypercalcemia: > 2.75mmol/l; HGB decreased more than 20g/L (not related to treatment or non mm factors); From the beginning of MM treatment, serum creatinine increased by more than 177umol / L (2mg / dl) and correlated with mm; Serum M protein associated hyperviscosity; The definition of recurrence after CR was at least one of the following: Immunofixation electrophoresis confirmed the presence of M protein in blood or urine; The proportion of bone marrow plasma cells was more than 5%; Any other manifestation of clinical progression (New plasmacytoma, osteolytic destruction, or hypercalcemia); (4) For the definition of disease progression, refer to the Chinese guidelines for the diagnosis and treatment of multiple myeloma, revised in 2020, and meet at least one of the following criteria: The increase of serum M protein should be more than or equal to 25% (the absolute value of increase must be >=5g/L); If the baseline serum M protein >=50g/L, the increase of M protein should be >=10g/L; Urine M protein increased by more than 25% (the absolute value of increase must be >=200mg/24h); If M protein in serum and urine can not be detected, the difference between serum and non involved FLC should be increased by more than 25% (the absolute value of increase must be >100mg/L); The percentage of bone marrow plasma cells increased by more than 25% (absolute value increased by more than 10%); The original bone lesions or soft tissue plasmacytoma increased by more than 25%, or new osteolytic lesions or soft tissue plasmacytoma appeared; Hypercalcemia associated with abnormal proliferation of plasma cells (adjusted serum calcium > 2.8 mmol/L or 11.5 mg/dl); Two consecutive efficacy evaluations must be performed before starting a new treatment; 5. ECOG=1x10^9/L; 8. Platelet count >=70x10^9/L; 9. Absolute lymphocyte count >=100 cells/uL; 10. Adequate organ function reserve: (1) ALT / AST =50% and no pericardial effusion were found by echocardiography; (4) Under the indoor natural air environment, the basic oxygen saturation is more than 92%. It
Exclusion criteria
Exclusion criteria: 1. Patients with other tumors (except non melanoma skin cancer and cervical cancer in situ, bladder cancer and breast cancer with disease-free survival of more than 5 years); 2. Patients with severe mental disorders; 3. Patients with grade III-IV heart failure or myocardial infarction, angioplasty or stent implantation, unstable angina pectoris or other heart diseases with prominent clinical symptoms within one year before enrollment; 4. Patients with any indwelling catheter or drainage tube (such as percutaneous nephrostomy tube, indwelling catheter, bile drainage tube or pleural / peritoneal / pericardial catheter) are allowed to use special central venous catheter; 5. Patients with central nervous system involvement or meningeal involvement of multiple myeloma; 6. Patients with positive results of any of the following virological tests: HIV; HCV; HBsAg; HBcAb positive; HBV DNA copy number positive; TPPA. 7. Patients with severe allergic history or allergic constitution; 8. Patients with severe underlying diseases, such as evidence of other severe active virus, bacterial infection or uncontrolled systemic fungal infection; active autoimmune disease or autoimmune disease history within 3 years; and; 9. Patients with autoimmune diseases (e.g. Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) with end organ injury or autoimmune diseases requiring systemic immunosuppressive / systemic disease regulation drugs in the past 2 years; 10. Patients with organ dysfunction, such as renal insufficiency; 11. Patients who have or are suffering from interstitial lung disease (e.g. pneumonia, pulmonary fibrosis); patients with known chronic obstructive pulmonary disease (COPD) and forced expiratory volume (FEV1) < 50% (normal value). Note that subjects suspected to have COPD must be tested for FEV1 and excluded if FEV1 < 50% (normal value). Subjects known to have moderate or severe persistent asthma in the past 2 years, or currently with uncontrollable asthma (any classification). (note that subjects currently suffering from controlled intermittent asthma or controlled mild persistent asthma were allowed to participate in the study); 12. Patients who have received other clinical trials within 4 weeks before participating in this trial; 13. Patients with poor compliance due to physiological, family, social, geographical and other factors, unable to cooperate with the study protocol and follow-up plan; 14. Patients who were contraindicated to cyclophosphamide or fludarabine chemotherapy; 15. Subjects who need to be treated with other immunosuppressive drugs within 72 hours before tcrt reinfusion, except for those used to treat adverse events during the trial; 16. Pregnant women, lactating women, men who have family planning during the study period or within 100 days after receiving the research treatment; 17. Any other condition considered unsuitable by the researchers.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| adverse events;severe adverse events;dose limited toxicity;maximum-tolerated dose; | — |
Secondary
| Measure | Time frame |
|---|---|
| complete remission;partial remission;objective response rate; | — |
Countries
China
Contacts
Public ContactPeng Liu
Zhongshan Hospital Affiliated to Fudan University
Outcome results
None listed