| Eligibility |
Inclusion Criteria:
1. Histologically confirmed: Diffuse Large B Cell Lymphoma (DLBCL), Transformation
Follicular Lymphoma (TFL), Primary Mediastinal Large B Cell Lymphoma (PMBCL) and
Mantle Cell Lymphoma (MCL), High-Grade B Cell Lymphoma (HGBL);
1. Refractory B-NHL: PD as the best response to normative first-line therapy
(intolerance of first-line therapy is not included in this study) or SD as the
best response to at least 4 courses of first-line therapy with duration no longer
than 6 month from last therapy; or PD as the best response to the last therapy of
second-line therapy and above,or SD as the best response to at least 2 courses of
second-line therapy with duration no longer than 6 month from last therapy, or:
2. Relapsed B-NHL: Histopathology confirmed relapse after standard systemic and
second-line therapy achieved CR, or histopathologically confirmed relapse within
1 year after autologous hematopoietic stem cell transplantation (Not limited by
previous therapy);
3. Prior therapy must include anti-CD20 monoclonal antibody (unless investigator
determines that tumor is CD20-negative) and an anthracycline;
4. For individual with TFL, must have chemotherapy and the conform the above
definition of relapse or refractory after transformation;
2. According to the 2014 Lugano therapy response standard, there should be at least one
measurable tumor focus: the longest diameter of nodular lesions> 1.5 cm, and the
longest diameter of extranodal lesions> 1.0 cm;
3. CD19 positive expression in tumor tissue biopsy;
4. Prior to apheresis, approved anti-B-NHL therapys such as systemic chemotherapy,
systemic radiotherapy and immunotherapy have been completed for at least 2 weeks;
5. Eastern cooperative oncology group (ECOG) performance status of 0 to 1;
6. Life expectancy =12 weeks;
7. Absolute neutrophil count (ANC)= 1×10^9/L;
8. Platelet count=50×10^9/L;
9. Absolute lymphocyte count (ALC)=1×10^8/L;
10. Adequate organ function defined as:
1. Serum ALT/AST =2.5 ULN;
2. Creatinine clearance (as estimated by Cockcroft Gault) =60 mL/min;
3. PT and APTT=1.5 ULN
4. Total bilirubin =1.5 ULN;
5. Cardiac ejection fraction =50%, no pericardial effusion, no clinically
significant ECG findings;
6. Baseline oxygen saturation >92% on room air;
11. Sufficient venous access for leukapheresis collection, and no other contraindications
to leukapheresis;
12. Female of childbearing age must agree to take effective contraceptive measures at
least 1 year after infusion; Male with fertile partners must agree to use effective
barrier contraceptive methods at least 1 year after infusion;
13. Understand and voluntarily sign the informed consent form.
Exclusion Criteria:
1. Diagnosis of other malignancy (except for cured non-melanoma skin cancer, cervical
carcinoma in situ, superficial bladder cancer, ductal carcinoma in situ, or other
malignancies that have completely responsed for more than 5 years);
2. Severe mental disorders;
3. History of hereditary diseases, including but not limited to: Fanconi anemia, Shut-Dai
syndrome, Costman syndrome or any other known bone marrow failure syndrome;
4. History of allogeneic stem cell transplantation;
5. Grade III-IV heart failure or myocardial infarction, angioplasty or stent placement,
unstableangina pectoris, or other clinically prominent heart disease within one year
before enrollment.
6. Have any indwelling catheter or drainage tube (such as percutaneous nephrostomy tube,
indwelling catheter, bile drainage tube or pleura / peritoneum / pericardial
catheter), the use of dedicated central venous catheter is allowed;
7. Subjects with CNS lymphoma, cerebrospinal fluid malignant cells or brain metastases;
8. History or presence of CNS disorder, including but not limited to: seizure disorder,
cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune
disease with CNS involvement;
9. Positive for any of the following etiological tests: HIV, HBV, HCV, TPPA;
10. Presence of fungal, bacterial, viral, or other infection that is uncontrolled;
11. Allergic subjects or subjects with severe allergic reactions to cyclophosphamide or
fludarabine;
12. History of autoimmune disease resulting in end organ injury or requiring systemic
immunosuppression/systemic disease modifying agents within the last 2 years;
13. History or diagnosis of pulmonary fibrosis;
14. Have received gene therapy or any other CAR-T treatment;
15. Have received any other drugs targeting CD19;
16. Subjects who received other clinical trial therapy within 4 weeks before participating
in this trial, or the informed consent form was signed within the 5 half-life of the
last administration in the other clinical trial (take longer time as standard);
17. Poor adherence due to physical, family, social, geographic, and other factors, who
cannot follow the research plan and follow-up plan;
18. Subjects with comorbidities that require systemic corticosteroid therapy (=5 mg/day of
prednisone or an equivalent dose of other corticosteroids) or other immunosuppressive
drugs within 6 months after study therapy according to the discretion of investigator;
19. Lactating women who are reluctant to stop breastfeeding;
20. Any other conditions defined by researcher that is inappropriate for the subject to be
enrolled.
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