Relapsed/refractory Multiple Myeloma
Conditions
Interventions
1×106 CAR+ cells/kg:Fully Human BCMA Chimeric Antigen Receptor Autologous T Cell Injection
Sponsors
Huazhong University of Science Tongji Hospital, Tongji Medical College
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Male or female patients aged 18 years old and above. 2. Diagnosis of MM with relapsed or refractory diseaseaccording to International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma. Enrolled patients had undergone at least 3 different prior lines of therapy (including chemotherapies based on proteasome inhibitor and immunomodulatory drugs). Induction chemotherapy, stem cell transplantation and maintenance therapy given continuously are considered as one line of therapy if no disease progression occurred during these treatment. Disease progression should occurred during the latest anti-myeloma treatment or within 12 months after the treatment. 3. Evidence of cell membrane BCMA expression, as determined by a validated immunohistochemistry (IHC) or a Flow Cytometry on tumor tissue (e.g., blood sample, bone marrow biopsies or plasmacytoma). 4. Subjects must have measurable disease, including at least one of the criteria below: 1) Bone marrow blast or monoclonal plasma cells = 5% of total bone marrow cells (Bone marrow cytometry, biopsies IHC or flow cytometry) . 2) Serum M-protein >=0.5 g/dL; 3) Urine M-protein >=200 mg/24 h; 4) FLC (Free Light Chain) type multiple myeloma with no other measurable disease detected in serum and urine: serum FLC>=10 mg/dL and Serum FLC kapa/gama ratio is abnormal; 5) Largest transverse diameter of extramedullary disease >=1 cm; 5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1; 6. Expected survival time >=12 weeks; 7. Subjects must have appropriate organ function and meet all of the following laboratory findings requirement before enrollment: 1) Hematology: Absolute neutrophil count (ANC) >1×10^9 /L; absolute lymphocyte count (ALC) >=0.3x10^9/L; platelets >=50x10^9/L; hemoglobin >60 g/L; 2) Liver function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =40 ml/min; 4) Coagulation function: Fibrinogen>=1.0g/L; activated partial thromboplastin time (APTT) 91%; 6) Left ventricular ejection fraction (LVEF) >=50%; 8. The subject and his/her spouse agree to take effective tools or contraception (excluding safe period contraception) from the signing of the ICF by the subject to one year after CAR T cell infusion; 9. All subjects or legal representatives must personally sign the informed consent form approved by the Ethics Committee in writing before starting any screening procedures.
Exclusion criteria
Exclusion criteria: 1. Patients with graft-versus-host disease (GVHD) or needing immunosuppressive agents; 2. Patients who have received hematopoietic stem cell transplantation (ASCT) or allogeneic hematopoietic stem cell transplantation (HSCT) within 12 weeks before leukapheresis; 3. Have mononuclear cells without activation by cytokine for leukapheresis; 4. Patients who have received the following anti-tumor treatment (before leukapheresis): 1) Targeted therapy, epigenetic therapy or use of invasive experimental medical devices within 14 days or at least 5 half-lives (whichever is longer), or; 2) Treatment of multiple myeloma with monoclonal antibodies within 21 days, or; 3) Cytotoxic or proteasome inhibitor treatment within 14 days, or; 4) Immunomodulatory treatment within 7 days; 5. Subjects who are receiving systemic steroid therapy within 7 days prior to screening or who require long-term systemic steroid therapy (except for inhalation or local use) during the treatment period determined by the investigators; 6. Patients with hypertension history whose disease is uncontrollable by drug therapy (blood pressure = 140/90 mmHg); 7. Severe cardiac diseases: including but not limited to unstable angina pectoris, myocardial infarction (within 6 months before screening), congestive heart failure (New York Heart Disease Association [NYHA] classification = Grade III) and severe arrhythmia; 8. Unstable systemic diseases judged by the investigators: including but not limited to severe liver, kidney or metabolic diseases requiring drug therapy; 9. Malignant tumors other than multiple myeloma within the 5 years prior to screening, except for fully treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical surgery, breast ductal carcinoma in situ after radical surgery; 10. Patients with a history of solid organ transplantation; 11. Patients with suspected or with a central nervous system invasion of plasma cell tumors; 12. Patients with solitary extramedulary plasmacytoma; 13. Patients having undergone major operation within 2 weeks before leukapheresis, or planning to receive surgery during the study or within 2 weeks after the study treatment is given (subjects planning to receive local anesthesia surgery can participate in this study); 14. Patients who are participating in other interventional clinical studies at the time of signing the ICF; 15. Active infection or uncontrollable infection requiring systemic treatment (except for mild genitourinary system infection and upper respiratory tract infection) exists within 7 days before leukapheresis; 16. The hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) is positive and the detection value of hepatitis B virus (HBV) DNA in peripheral blood is more than 100 IU/mL. The hepatitis C virus (HCV) antibody is positive and the peripheral blood HCV RNA is positive. The human immunodeficiency virus (HIV) antibody is positive. The cytomegalovirus (CMV) DNA is positive. The syphilis test is positive; 17. Pregnant or lactating women; 18. Patients with mental disease or impairment of consciousness; 19. Patients with other conditions regarded by other investigators as not suitable for enrollment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Serum calcium & albumin corrected calcium;Beta 2-microglobulin;Serum immunoglobulin quantification;Serum protein electrophoresis;Serum immunofixation electrophoresis;Urine protein electrophoresis;Urinary protein immunofixation electrophoresis; | — |
Countries
China
Contacts
Public ContactChunrui Li
Huazhong University of Science Tongji Hospital, Tongji Medical College
Outcome results
None listed