Autologous Cells Derived Anti-CD19 CAR-Engineered T Cells With Concurrent BTK Inhibitor for B Cell Lymphoma
Diffuse Large B Cell Lymphoma, Burkitt Lymphoma, Follicular Lymphoma
About this trial
This is an interventional treatment trial for Diffuse Large B Cell Lymphoma
Eligibility Criteria
Inclusion Criteria:
- Aged ≥ 18 years and <70 years.
- Expected survival over 6 months.
- Eastern Cooperative Oncology Group score≤ 2.
- Diagnosed pathologically and histologically CD19+B cell lymphoma, including mantle cell lymphoma, chronic lymphocytic leukemia, follicular cell lymphoma, Burkitt lymphoma and diffuse large B cell lymphoma.
- Patients have failed at least 1 line of prior therapy
- Negativity of blood pregnancy test for woman, and participants use effective methods of contraception until last follow-up.
Patient or his or her legal guardian voluntarily participates in and signs an informed consent form.
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Exclusion Criteria:
- Investigators judge the patients with gastrointestinal lymph node and/or central nervous system involvement who may be at high-risk of receiving CAR-T-CD19 cell treatment.
- Existing or preexisting CNS conditions, such as epileptic seizures, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any CNS related autoimmune diseases.
- Patients with graft-versus-host reaction and need immunosuppressive agents, or patients with autoimmune diseases.
- Participants with other active malignancies (except non-melanoma skin cancer and cervical cancer) within five years.
- History of Richter's syndrome.
- History of any one of the following cardiovascular conditions within the past 6 months: Class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease.
- Patients who are pregnant or breast-feeding.
Patients with any one of the following terms:
A. Creatine >2.5mg/dl (221.0umol/L). B. Alanine aminotransferase/aspartate aminotransferase >3 times the upper limit of normal (ULN).
C. Total bilirubin>2.0 mg/dl (34.2umol/L).
- Major surgery within 4 weeks of randomization.
- Systemic steroids are used within 2 weeks before apheresis (Except for those who are using inhaled steroids recently or currently).
- Patients receive cytotoxic chemotherapy or radiotherapy within 21 days before enrollment (Tyrosine kinase inhibitors or other targeted therapies can be used two weeks before lymphodepleting chemotherapy).
- Prior treatment with any gene therapy product.
- Active hepatitis B, active hepatitis C, or active human immunodeficiency virus (HIV) infection.
- Systemic fungal, bacterial, viral, or other infection that is not controlled.
- The absolute value of lymphocytes was too low to manufacture CAR-T cells.
Other conditions considered inappropriate by the researcher.
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Sites / Locations
- Union Hospital, Huazhong University of Science and TechnologyRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Effective of CAR-T-CD19 cells with concurrent BTK inhibitor
Effective of CAR-T-CD19 cells monotherapy
After enrollment, all subjects will receive oral BTK inhibitor immediately and BTK inhibitor treatment will continue for up to 90 days (or longer for who are benefiting from BTK inhibitor) after CAR-T-CD19 infusion. Eligible patients will undergo leukapheresis to obtain peripheral blood mononuclear cells (PBMCs) for CAR T-cell production. Upon successful generation CAR-T-CD19 product, participants will receive fludarabine-based lymphodepletion chemotherapy, followed by infusion of CAR-T-CD19 cells (2*10^6 cells/kg) on day 0 and day 1 respectively.
Eligible patients will undergo leukapheresis to obtain peripheral blood mononuclear cells (PBMCs) for CAR T-cell production. Upon successful generation CAR-T-CD19 product, participants will receive fludarabine-based lymphodepletion chemotherapy, followed by infusion of CAR-T-CD19 cells (2*10^6 cells/kg) on day 0 and day 1 respectively.