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

NCT ID: NCT05745181

Last Updated: 2023-02-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-02-01
• Study Completion Date: 2026-01-01

Brief 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.

Conditions

Acute T-lymphoblastic Leukemia; Acute T-lymphoblastic Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CAR-T Cell Infusion

Peripheral blood mononuclear cells were isolated, amplified and cultured in vitro, pretreated with FC regimen, and Anti-CD1a CAR-T cells were transfused.

Group Type: EXPERIMENTAL

CAR-T Cell Infusion

Intervention Type: BIOLOGICAL

Peripheral blood mononuclear cells were isolated, amplified and cultured in vitro, pretreated with FC regimen, and Anti-CD1a CAR-T cells were transfused.

Interventions

CAR-T Cell Infusion

Peripheral blood mononuclear cells were isolated, amplified and cultured in vitro, pretreated with FC regimen, and Anti-CD1a CAR-T cells were transfused.

Intervention Type: BIOLOGICAL

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.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Affiliated Hospital of Xuzhou Medical University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

The Affiliated Hospital of Xuzhou Medical University

Xuzhou, Jiangsu, China

Site Status: RECRUITING

Countries

China

Central Contacts

Wei Sang, M.D., Ph.D.

Role: CONTACT

xyfylbl515@xzhmu.edu.cn

13645207648

Facility Contacts

Wei Sang, M.D., Ph.D.

Role: primary

xyfylbl515@xzhmu.edu.cn

13645207648

Other Identifiers

XYFY2022-KL479-01

Identifier Type: -

Identifier Source: org_study_id