Overview
This is a single-center, open-label, single-arm study to evaluate the primary safety and efficacy of anti-CD7 chimeric antigen receptor(CAR)-modified T cells(CAR7-Ts) in patients with relapsed or refractory T lymphoid malignancies.
Description
Chimeric antigen receptor-T cells (CAR-T) have made breakthroughs in the treatment of B-cell tumors, especially refractory/relapsed acute B lymphocytes. CD7 is a transmembrane glycoprotein expressed by T cells and natural killer cells and their precursors; it is also expressed in >95% of lymphoblastic T-cell leukemias and lymphomas . CD7 was previously evaluated as a target for immunotoxin-loaded antibodies in patients with T-cell malignancies, but tumor responses were limited.
Enhancing the potency of CD7-directed cytotoxicity by substituting donor-derived CAR-T cells for a monoclonal antibody would augment the efficacy of CD7-targeted therapy in patients with T-cell malignancies. To prepare CAR7-T cells, CD7 expression is suppressed on donor-derived T cells by unique blocking technique, and CD7-negative T cells are transduced with a humanized anti-CD7-41BB-CD3ζ lentiviral vector.
This is an investigational study. The objectives are to evaluate the safety and efficacy of CAR7-T cells in patients with CD7+ T-cell malignancies.
Eligibility
Inclusion Criteria:
- Aged from 14 to 70 years;
- Expected survival over 60 days;
- Eastern Cooperative Oncology Group score 0-2;
- Diagnosed as T-cell hematologic malignancies (including leukemia and lymphoma) according to WHO2016 criteria;
- Patients must relapse or be refractory after at least two lines of therapy.
- CD7 were positive in bone marrow or cerebrospinal fluid by immunohistochemistry or
flow cytometry at screening, and one of the following conditions is satisfied:
- No remission was achieved after at least 2 lines of standard therapy; B. Relapse or progression after standard treatment; C. Relapse after autologous or allogeneic hematopoietic stem cell transplantation;
- Have no fertility requirements or plans for one year since enrollment in this clinical
trial;
- Patient or his or her legal guardian voluntarily participates in and signs an informed consent form.
Exclusion Criteria:
- Complicated with central system leukemia/lymphoma with active intracranial lesions;
- Existing or preexisting CNS conditions, such as epileptic seizures, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any CNS related autoimmune disease;
- Symptomatic heart failure or severe arrhythmias;
- Symptoms of severe respiratory failure;
- Complicated with other types of malignant tumors;
- Serum creatinine and/or urea nitrogen ≥ 1.5 times of normal value;
- Suffer from sepsis or other uncontrollable infections;
- Intracranial hypertension or brain consciousness disorder;
- Severe mental disorders;
- Have received organ transplantation (excluding bone marrow transplantation);
- Female patients (fertile patients) had positive blood HCG test;
- Hepatitis (including hepatitis B and C), AIDS and syphilis were screened positive;
- Patients with graft-versus-host disease (GVHD) or who require immunosuppressant treatment;
- The absolute value of lymphocytes was too low to manufacture CART cells;
- Other conditions considered inappropriate by the researcher.
