Hematologic Malignancy
Conditions
Keywords
CD7, CAR-T
Brief summary
This study is a single-center, open, prospective single-arm clinical study of patients with CD7 postive relapsed / refractoryhematological tumors to evaluate the safety and efficacy of CD7-specific CAR-T cells in relapsed / refractory hematological tumors while collecting pharmacokinetics and pharmacodynamics indicators of CAR-T cells.
Detailed description
In order to study CD7-targeting CAR-T cell therapy, we constructed a lentiviral CAR structure. The CD7-targeting fragment was cloned into a second-generation CAR structural backbone with 4-1BB and CD3E. Since endogenous CD7 in T cells causes CD7-targeting CAR-T cells to kill each other, we used a natural selection method to prepare CD7-targeting CAR (CD7-CART) T cells that do not express the CD7 protein (CD7-).
Interventions
DRUGFludarabine + Cyclophosphamide + CD7-specific CAR-T Cells
fludarabine 30 mg/kg on day -5, -4, and -3; cyclophosphamide 300 mg/kg on day -5, -4, and -3; CD7-specific CAR-T Cells on day 0.
Sponsors
Hebei Taihe Chunyu Biotechnology Co., Ltd
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Subjects with a diagnosis of relapsed/refractory hematologic malignancies that meet any of the following criteria: 1. Recurrence: peripheral blood or bone marrow blasts (proportion\>5%) after achieving complete remission after previous standard treatment regimens, or extramedullary disease, including: i) Early recurrence within 12 months; ii) Late recurrence of 12 months or more with no remission after one course of standard induction chemotherapy; iii) Relapse after autologous or allogeneic hematopoietic stem cell transplantation. 2. Refractory: complete remission is not achieved after at least two courses of standard induction therapy, or complete remission is not achieved after first-line or above salvage therapy * At the time of enrollment screening, bone marrow flow cytometry detected tumor cells as CD7 expression and/or pathological immunohistochemistry of extramedullary lesions was confirmed that tumor cells expressed CD7. * If tumor cells are detected in peripheral blood during enrollment screening, the immunophenotype of tumor cell surface at the time of flow cytometry detection should be CD4 and CD8 negative. If the surface immunophenotype of peripheral blood tumor cells is not CD4 and CD8 negative, the condition of ≤1% proportion of peripheral blood tumor cells must be met. * Subjects with the Eastern Cooperative Oncology Group (ECOG) fitness scores of 0 to 2. * Expected survival over 3 months; * Liver, kidney and cardiopulmonary functions meet the following requirements: 1. Serum creatinine ≤ 1.5× ULN； 2. Left ventricular ejection fraction (LVEF) ≥50%; 3. Baseline peripheral oxygen saturation \> 90%; 4. Total bilirubin ≤ 1.5×ULN; ALT and AST ≤2.5×ULN. * Patient or his or her legal guardian voluntarily participates in and signs an informed consent form.
Exclusion criteria
* Appearance of one of the following cardiac criteria: atrial fibrillation; myocardial infarction in the last 12 months; prolonged QT syndrome or secondary QT extension, as judged by the investigator. Echocardiography LVSF \<30% or LVEF \<50%; clinically significant pericardial effusion; cardiac insufficiency NYHA (New York Heart Association) III or IV (confirmed by echocardiography within 12 months of treatment). * Active GVHD. * History of severe pulmonary function impairment disease. * Other malignant tumors in the advanced stage. * Severe infection or persistent infection that cannot be effectively controlled. * Combined with severe autoimmune disease or innate immune deficiency. * Active hepatitis (hepatitis B virus deoxyribonucleic acid \[HBV-DNA 500 IU / ml and abnormal liver function\] or hepatitis C antibody \[HCV-Ab\] positive, HCV-RNA above the lower limit of detection of the analytical method and abnormal liver function). * Human immunodeficiency virus (HIV) infection or syphilis infection. * History of severe allergies to biological products (including antibiotics). * Central nervous system disorders, such as uncontrolled epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar diseases, etc.. * Female patients are in pregnancy and lactation, or have a pregnancy plan within 12 months. * Situations where the investigator may increase the risk or interfere with the test results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) of administering CD7-specific CAR-T Cells In the treatment of relapsed/refractory hematologic tumors | within 3 years after infusion | Disease overall response rate (ORR) will be assessed from CAR-T cell infusion to death or last follow-up (censored). |
| Incidence of Treatment-related Adverse Events | Within 3 month after CD19&CD20 CAR-T infusion | Therapy-related adverse events (AE), including severe adverse events (SAE) and laboratory outliers with clinical significance, will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| In vivo expansion and survival of CD7-specific CAR-T Cells in relapsed/refractory hematological malignancies | within 3 years after infusion | Quantity of CD7 CAR copies in bone marrow, peripheral blood and cerebrospinal fluid will be determined by using flow cytometry and quantitative polymerase chain reaction. |
Countries
China
Contacts
Primary ContactMei Heng, M.D., Ph.D
Backup ContactYun Kang
Outcome results
None listed