Clinical Study of Anti-CD1a CAR-T in the Treatment of R/R Acute T-lymphoblastic Leukemia/Lymphoblastic Lymphoma

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of anti-CD1a CAR-T in the treatment of relapsed refractory acute T-lymphoblastic leukemia/lymphoblastic lymphoma.

Detailed Description
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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.

Official Title
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Clinical Study of Anti-CD1a CAR-T in the Treatment of Relapsed Refractory Acute T-lymphoblastic Leukemia/Lymphoblastic Lymphoma

Conditions
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Acute T-lymphoblastic Leukemia, Acute T-lymphoblastic Lymphoma

Intervention / Treatment
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* Biological: CAR-T Cell Infusion


Participation Criteria
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Eligibility Criteria
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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 Patients or their legal guardians voluntarily participate and sign the informed consent; Male or female patients aged 18-70 years (including 18 and 70 years); 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. The following two categories are included: (1) CD1a+T lymphoblastic lymphoma (T-LBL); (2) CD1a+ acute T-lymphoblastic leukemia (T-ALL). 5. Subject: There was no remission or residual lesions after treatment, and HSCT (auto/allo-HSCT) was not suitable; Relapse occurred after CR, and HSCT (auto/allo-HSCT) was not suitable; Patients with high risk factors; 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: Liver function: ALT/AST < 3 times the upper limit of normal (ULN) and total bilirubin ≤34.2μmol/L; Renal function: creatinine < 220 μmol/L; Lung function: indoor oxygen saturation ≥95%; 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: There was no remission or residual lesions after treatment, and HSCT (auto/allo-HSCT) was not suitable; Relapse occurred after CR, and HSCT (auto/allo-HSCT) was not suitable; Patients with high risk factors; 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: Liver function: ALT/AST < 3 times the upper limit of normal (ULN) and total bilirubin ≤34.2μmol/L; Renal function: creatinine < 220 μmol/L; Lung function: indoor oxygen saturation ≥95%; 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: Women who are pregnant (urine/blood pregnancy test positive) or breastfeeding; Men or women who have planned to become pregnant within the last 1 year; The patients were not guaranteed to take effective contraceptive measures (condoms or contraceptives, etc.) within 1 year after enrollment; Patients had uncontrollable infectious diseases within 4 weeks prior to enrollment; Active hepatitis B/C virus; Hiv-infected patients; Suffering from a serious autoimmune disease or immunodeficiency disease; The patient is allergic to antibodies, cytokines and other macromolecular biological drugs; The patient had participated in other clinical trials within 6 weeks prior to enrollment; Systemic use of hormones within 4 weeks prior to enrollment (except for inhaled hormones); Suffers from mental illness; The patient has substance abuse/addiction; According to the researchers judgment, the patient had other conditions that were not suitable for inclusion.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CAR-T Cell Infusion<br>Peripheral blood mononuclear cells were isolated, amplified and cultured in vitro, pretreated with FC regimen, and Anti-CD1a CAR-T cells were transfused. | Biological: CAR-T Cell Infusion<br>* Peripheral blood mononuclear cells were isolated, amplified and cultured in vitro, pretreated with FC regimen, and Anti-CD1a CAR-T cells were transfused.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate | CR+PR | From 2 weeks to 1 year. | 
| Progression-free survival | The time between treatment and observation of disease progression or death from any cause. | From 2 weeks to 1 year. | 
| overall survival | The time interval between patient infusion of CAR-T and death from any cause or the end of follow-up. | From 2 weeks to 1 year. | 
| Event-free survival | The time from the start of CAR-T infusion to the occurrence of any event. | From 2 weeks to 1 year. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterization of the level of CAR T cell expansion in subjects over time | Characterization of the level of CAR T cell expansion in subjects over time. | From 2 weeks to 1 year. | 
| Duration of CAR T cells in subjects | Duration of CAR T cells in subjects | From 2 weeks to 1 year. | 
| Characteristics of lymphocyte reduction in subjects | Characteristics of lymphocyte reduction in subjects | From 2 weeks to 1 year. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anti-CD1a CAR-T, relapsed refractory