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

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

NCT ID: NCT05745181

Condition: Acute T-lymphoblastic Leukemia
Acute T-lymphoblastic Lymphoma

Conditions: Official terms:
Lymphoma
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Lymphoma, Non-Hodgkin

Conditions: Keywords:
anti-CD1a CAR-T
relapsed refractory

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Biological
Intervention name: CAR-T Cell Infusion
Description: Peripheral blood mononuclear cells were isolated, amplified and cultured in vitro, pretreated with FC regimen, and Anti-CD1a CAR-T cells were transfused.
Arm group label: CAR-T Cell Infusion

Summary: 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: 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.

Criteria for 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.

Gender: All

Minimum age: 18 Years

Maximum age: 70 Years

Healthy volunteers: No

Locations:

Facility:
Name: The Affiliated Hospital of Xuzhou Medical University

Address:
City: Xuzhou
Zip: 221002
Country: China

Status: Recruiting

Contact:
Last name: Wei Sang, M.D., Ph.D.

Phone: 13645207648
Email: xyfylbl515@xzhmu.edu.cn

Start date: February 1, 2023

Completion date: January 1, 2026

Lead sponsor:
Agency: The Affiliated Hospital of Xuzhou Medical University
Agency class: Other

Source: The Affiliated Hospital of Xuzhou Medical University

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05745181