Cord Blood Derived Anti-CD19 CAR-Engineered NK Cells for B Lymphoid Malignancies
Acute Lymphocytic Leukemia, Chronic Lymphocytic Leukemia, Non Hodgkin's Lymphoma
About this trial
This is an interventional treatment trial for Acute Lymphocytic Leukemia
Eligibility Criteria
Inclusion Criteria:
- Aged ≥ 18 years;
- Eastern Cooperative Oncology Group score≤ 3;
- Diagnosed as CD19+ B-cell hematological malignancies, including acute lymphoblastic leukemia, chronic lymphocytic leukemia and Non Hodgkin's lymphoma.
- Patients must relapse or be refractory after at least two lines of therapy.
Patient's main organs functioning well:
A. Liver function: alanine aminotransferase/aspartate aminotransferase < 2.5 times the upper limit of normal (ULN) and total bilirubin≤ 1.5 times ULN; B. Renal function: Creatinine clearance rate ≥ 60ml/min. C. Pulmonary function: Indoor oxygen saturation ≥ 95%. D. Cardiac Function: Left ventricular ejection fraction (LVEF) ≥50%, no clinically-significant ECG findings.
- 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.
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-NK-CD19 cell treatment.
- Patients with graft-versus-host reaction and need immunosuppressive agents, or patients with autoimmune diseases.
- Systemic steroids are used within 5 days before apheresis.
- Drugs to stimulate the production of bone marrow hematopoietic cells are used within 5 days before apheresis.
- 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).
- History of epilepsy or other central nervous system diseases.
- Participants with other active malignancies (except non-melanoma skin cancer and cervical cancer) within five years.
- Known HIV positive patients.
- Patients with active infections, including active replication of hepatitis B or active hepatitis C.
- Patients receive any antitumor treatments within 4 weeks before enrollment, and the toxicity related to previous treatments don't return to < 1 level at enrollment (except for low grade toxicity such as alopecia).
- Major surgery in the past 4 weeks.
- Non-compliant patients.
- Anticoagulants are being used.
Sites / Locations
- Union Hospital, Huazhong University of Science and TechnologyRecruiting
Arms of the Study
Arm 1
Experimental
Fludarabine + Cyclophosphamide + CAR-NK-CD19 Cells
Patients will received lymphodepletion with fludarabine (30 mg/kg) and cyclophosphamide (300 mg/kg) on day -5, -4, and -3, followed by one infusion of CAR-NK-CD19 cells on day 0. The study will be divided into three groups: Acute Lymphocytic Leukemia, Chronic Lymphocytic Leukemia, and Non Hodgkin's Lymphoma. Doses of 0.01×10^7, 0.1×10^7, 1.0×10^7 CAR+ T cells (with an allowance of ±20%) will be tested in each group in the 3+3 dose-escalation study. Each dose group has 3 patients. If no dose-limited toxicity (DLT) emerges in the group, then the subsequent higher dose will be used in the next group. If DLT emerges in a single subject in any dose level, 3 more subjects will be enrolled to the same dose level. The maximum dose could be extended.