Breast Cancer
Conditions
Interventions
Case series:MUC-1 CAR Tcell
Sponsors
The Second Affiliated Hospital of Zhejiang University
Eligibility
Sex/Gender
Female
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: 1. Female aged 18 - 65 years old; Pathological diagnosis is breast cancer; 3. metastatic breast cancer, previously received at least 2-4 chemotherapy or multi-line endocrine therapy, there is no standard treatment; 4. MUC-1 expression =1 + as determined by immunohistochemistry (IHC) in a laboratory accredited by the sponsor; 5. According to RECIST 1.1 version of the standard has at least one measles extracranial measurable lesions have not received radiotherapy; 6. Chemotherapy, radiotherapy, molecular boot therapy and surgery were not received within 4 weeks prior to the study start-up and have been rescued from acute toxic reactions previously treated except for hair loss and peripheral neurotoxicity; 7. Expected survival of = 6 months; 8. Asymptomatic brain metastases, or brain metastases that have undergone topical (surgery / radiotherapy) therapy prior to study onset, are clinically stable for at least 8 weeks; 9. The main organs function properly, that is, meet the following criteria: 1) The ECOG physical status score is 0-2 2) Blood test should meet the following criteria: HB=90g / L (no blood transfusion within 14 days); ANC=1.5 × 10 ^ 9 / L; PLT=80 × 10 ^ 9 / L; 3) biochemical tests should meet the following criteria: TBIL=1.5 x ULN (upper limit of normal); ALT and AST=2.5 x ULN; ALT and AST=5xULN if liver metastases; serum Cr=1xULN, endogenous creatinine clearance > 50 ml / min (Cockcroft-Gault formula); 10. Women of childbearing age must have a pregnancy test (serum or urine) within 7 days before enrollment and the result is negative and are willing to use appropriate methods of contraception either during the experiment and 8 weeks after the last dose of CART (subject to sterilization or menopause Women who have been at least 2 years old can be considered as having no fertility); 11. Participants voluntarily joined the study, signed informed consent, compliance is good, with follow-up.
Exclusion criteria
Exclusion criteria: 1. In the past 5 years there is other malignant tumor history, but the cured skin basal cell carcinoma and cervical carcinoma in situ except; 2. Previously received MUC-1 targeted therapy, chimeric antigen receptor therapy, or other transgenic T cell therapy; 3. Pregnant or lactating women; 4. Participate in other drug clinical trials within 4 weeks before the study begins; 5. Patients with hypertension who are not well controlled by a single antihypertensive medication (systolic> 140 mmHg, diastolic> 90 mmHg), patients with grade I or higher myocardial ischemia or myocardial infarction, grade I and above arrhythmias Including QT interval = 440ms) or complete cardiac function; 6. Long-term unhealed chest or other parts of the wound or fracture; 7. Those with history of abuse of psychotropic substances who can not be abstinent or who have mental disorders; 8. Past and current patients with objective evidence of a history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-associated pneumonia, severely impaired pulmonary function; 9. There are fungi, bacteria, viruses or other infections that are uncontrollable or require IV antibacterial therapy. If there is a response to active therapy, a simple urinary tract infection and no complication of bacterial pharyngitis are allowed after consultation with the medical examiner; 10. For subjects with previously used chemotherapy, =2 hematologic toxicity or =3 non-hematologic toxicity at enrollment according to NCI-CTCAE 4.0 criteria; 11. A known history of HIV or Hepatitis B (HBsAg positive) or Hepatitis C virus (anti-HCV positive) infection is known; 12. There are any indwelling catheters or drains (eg, percutaneous nephrostomy tubes, indwelling Foley catheters, bile ducts, or pleural / peritoneal / pericardial catheters). Allow use of a dedicated central venous catheter; 13. brain metastasis or uncontrollable brain metastases; 14. There is a CNS history or disease, such as seizure disease, cerebrovascular ischemia / hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving CNS; 15. There was a history of myocardial infarction, angioplasty or stenting, unstable angina or other clinically significant heart disease within the 12-month period, New York Heart Association (NYHA) class III or IV heart failure ; 16. There is a significant immunodeficiency; 17. Have a history of severe hypersensitivity reactions to the major therapeutic agents used in this study, including fludarabine, cyclophosphamide, mesna, and tocilizumab and anti-infectives for CRS during the pretreatment period; 18. The group had a history of deep venous thrombosis or pulmonary embolism within 6 months; 19. Any woman who is fertile or pregnant while breastfeeding. Women who have undergone sterilization or have been at least 2 years post-menopausal may be considered non-fertile; 20. A history of autoimmune diseases (eg, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) that cause damage to the terminal organ or that require systemic immunosuppression / systemic disease modulation over the past two years; 21. Any disease that may interfere with the safety of the study treatment or assessment of efficacy; 22. Female subjects who are unwilling to take birth control 6 months after signing the consent form and from completing the CART administration.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PET CT; | — |
Countries
China
Contacts
Public ContactJian Huang
Second Affiliated Hospital of Zhejiang University
Outcome results
None listed