clinical study of anti-cd1a car-t in the treatment of r/r acute t-lymphoblastic leukemia/lymphoblastic lymphoma

Conditions: Acute T-lymphoblastic Leukemia; Acute T-lymphoblastic Lymphoma

Summary: to evaluate the efficacy and safety of anti-cd1a car-t in the treatment of relapsed refractory acute t-lymphoblastic leukemia/lymphoblastic lymphoma.

acute t-lymphoblastic leukemia/lymphoblastic lymphoma (t-all/lbl) is a highly heterogeneous hematological malignancy usually associated with genetic alterations/mutations in transcription factors that are major regulators of hematopoietic stem/progenitor cell homeostasis and t cell development. 70% of patients develop mass with myeloid invasion and other leukemia symptoms. cd1a, a transfer membrane glycoprotein, is a cell surface antigen present on cortical t-all cells. it is present in 40% of t-all cases. specific expression of this antigen has also been observed in developing cortical thymus cells. it was also slightly expressed in langerhans cells, digital dendritic cells, b lymphocytes and gastrointestinal epithelial cells. cd1a4 was not expressed in cd34+ progenitor cells or t cells during ontogeny. this property of cd1a makes it a suitable target antigen whose targeting minimizes the possibility of non-tumor toxicity. this study intends to treat r/r cd1a+t-all/lbl with cd1a car-t to observe its safety and efficacy.

Eligibility criteria:
inclusion criteria: 1. patients or their legal guardians voluntarily participate and sign the informed consent; 2. male or female patients aged 18-70 years (including 18 and 70 years); 3. the patient was diagnosed with cd1a+ acute t lymphoblastic leukemia/lymphoblastic lymphoma by pathology or flow cytometry, and had no effective treatment options at present, such as chemotherapy or hematopoietic stem cell transplantation after recurrence; alternatively, the patient voluntarily chooses to administer anticd1a-car t cells as salvage therapy. inclusion criteria 1. patients or their legal guardians voluntarily participate and sign the informed consent; 2. male or female patients aged 18-70 years (including 18 and 70 years); 3. the patient was diagnosed with cd1a+ acute t lymphoblastic leukemia/lymphoblastic lymphoma by pathology or flow cytometry, and had no effective treatment options at present, such as chemotherapy or hematopoietic stem cell transplantation after recurrence; alternatively, the patient voluntarily chooses to administer anticd1a-car t cells as salvage therapy. 4. the following two categories are included: (1) cd1a+t lymphoblastic lymphoma (t-lbl); (2) cd1a+ acute t-lymphoblastic leukemia (t-all). 5. subject: 1. there was no remission or residual lesions after treatment, and hsct (auto/allo-hsct) was not suitable; 2. relapse occurred after cr, and hsct (auto/allo-hsct) was not suitable; 3. patients with high risk factors; 4. relapse or no remission after hematopoietic stem cell transplantation or cellular immunotherapy. 6. measurable or evaluable lesions; 7. the patient's main tissues and organs function well: 1. liver function: alt/ast \< 3 times the upper limit of normal (uln) and total bilirubin ≤34.2μmol/l; 2. renal function: creatinine \< 220 μmol/l; 3. lung function: indoor oxygen saturation ≥95%; 4. cardiac function: left ventricular ejection fraction (lvef) ≥40%. 8. the patients had not received any anti-cancer treatment such as chemotherapy, radiotherapy, immunotherapy (such as immunosuppressive drugs) within the first 4 weeks of enrollment, and their previous treatment-related toxic reactions had recovered to ≤ grade 1 at the time of enrollment (except low toxicity such as hair loss); 9. the patient's peripheral shallow venous blood flow is smooth, which can meet the needs of intravenous infusion; 10. patients with ecog score ≤2 and expected survival time ≥3 months. 4. the following two categories are included: (1) cd1a+t lymphoblastic lymphoma (t-lbl); (2) cd1a+ acute t-lymphoblastic leukemia (t-all). 5. subject: 1. there was no remission or residual lesions after treatment, and hsct (auto/allo-hsct) was not suitable; 2. relapse occurred after cr, and hsct (auto/allo-hsct) was not suitable; 3. patients with high risk factors; 4. relapse or no remission after hematopoietic stem cell transplantation or cellular immunotherapy. 6. measurable or evaluable lesions; 7. the patient's main tissues and organs function well: 1. liver function: alt/ast \< 3 times the upper limit of normal (uln) and total bilirubin ≤34.2μmol/l; 2. renal function: creatinine \< 220 μmol/l; 3. lung function: indoor oxygen saturation ≥95%; 4. cardiac function: left ventricular ejection fraction (lvef) ≥40%. 8. the patients had not received any anti-cancer treatment such as chemotherapy, radiotherapy, immunotherapy (such as immunosuppressive drugs) within the first 4 weeks of enrollment, and their previous treatment-related toxic reactions had recovered to ≤ grade 1 at the time of enrollment (except low toxicity such as hair loss); 9. the patient's peripheral shallow venous blood flow is smooth, which can meet the needs of intravenous infusion; 10. patients with ecog score ≤2 and expected survival time ≥3 months. exclusion criteria: 1. women who are pregnant (urine/blood pregnancy test positive) or breastfeeding; 2. men or women who have planned to become pregnant within the last 1 year; 3. the patients were not guaranteed to take effective contraceptive measures (condoms or contraceptives, etc.) within 1 year after enrollment; 4. patients had uncontrollable infectious diseases within 4 weeks prior to enrollment; 5. active hepatitis b/c virus; 6. hiv-infected patients; 7. suffering from a serious autoimmune disease or immunodeficiency disease; 8. the patient is allergic to antibodies, cytokines and other macromolecular biological drugs; 9. the patient had participated in other clinical trials within 6 weeks prior to enrollment; 10. systemic use of hormones within 4 weeks prior to enrollment (except for inhaled hormones); 11. suffers from mental illness; 12. the patient has substance abuse/addiction; 13. according to the researchers judgment, the patient had other conditions that were not suitable for inclusion.

Keywords: anti-cd1a car-t relapsed refractory