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

Sponsor

The Affiliated Hospital of Xuzhou Medical University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05745181

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute T-lymphoblastic Leukemia Acute T-lymphoblastic Lymphoma	Biological: CAR-T Cell Infusion	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 1, 2023

Anticipated Primary Completion Date :

Jan 1, 2026

Anticipated Study Completion Date :

Jan 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Biological: 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.

Arm

Intervention/Treatment

Experimental: 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.

Biological: 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.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Characterization of the level of CAR T cell expansion in subjects over time [From 2 weeks to 1 year.]
Characterization of the level of CAR T cell expansion in subjects over time.
Duration of CAR T cells in subjects [From 2 weeks to 1 year.]
Duration of CAR T cells in subjects
Characteristics of lymphocyte reduction in subjects [From 2 weeks to 1 year.]
Characteristics of lymphocyte reduction in subjects

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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); 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.
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.
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.