Clinical Study of CAR-iNKT Cells in the Treatment of Relapsed/Refractory/High-risk B-cell Tumors

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

Clinical Study of CAR-iNKT Cells in the Treatment of Relapsed/Refractory/High-risk B-cell Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04814004
• Other study ID #: XYFY2021-KL062
• Status: Recruiting
• Phase: Phase 1
• Start date: March 19, 2021
• Est. completion date: April 1, 2024

Study information

• Verified date: March 2021
• Source: Xuzhou Medical University
• Contact: Jiang Cao, Ph.D
• Phone: 86-516-85802007
• Email: zimu05067[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to evaluate the safety and feasibility of hCD19.IL15.CAR-iNKT cells in treating patients with relapsed/refractory/high-risk B-cell tumors.

Description:

CD19 CAR-T has been shown to treat a variety of refractory or recurrent B-cell tumors. Because most CAR-T cells are generated from the patient's own T cells and are individualized products, and there are individual differences between patients, the generation of customized CAR-T cells is an expensive and time-consuming process. Universal CAR- iNKT cells are an ideal product for cell therapy. In this study, we prepared universal iNKT cells expressing hCD19 CAR and IL-15 to treat refractory, relapsed, or high-risk B-cell tumors.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: April 1, 2024
• Est. primary completion date: April 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 70 Years

Eligibility

Inclusion Criteria:

• Male or female patients aged 5-70 years;
• The patient's ECOG score was =2, and the expected survival time of > was 12 weeks.
• The patient was diagnosed with B-cell tumor by pathological and histological examination and had no effective treatment options, such as recurrence after chemotherapy or hematopoietic stem cell transplantation. Or the patient voluntarily chooses the infusion of CAR-INKT cells as the first treatment.
• B cell tumors include the following three types:

1. B-cell acute lymphocytic leukemia (B-ALL);

2. Inert B-cell lymphoma (CLL, FL, MZL, LPL, HCL);

3. Aggressive B-cell lymphoma (DLBCL, BL, MCL);

• Subject:

1. Residual lesions remain after primary treatment and are not suitable for HSCT (Auto/Allo-HSCT);

2. relapse after complete response (CR1) and unsuitable for allogeneic/autologous HSCT;

3. Patients with high risk factors;

4. relapse or no remission after hematopoietic stem cell transplantation or cellular immunotherapy.

• having measurable or evaluable lesions;
• The main tissues and organs of the patient function well:

1. Liver function: ALT/AST < 3 times the upper limit of normal (ULN);

2. Renal function: creatinine < 220µmol/L;

3. Lung function: indoor oxygen saturation =95%;

4. Heart function: left ventricular ejection fraction (LVEF) =40%.

• Patients or their legal guardians voluntarily participate and sign the informed consent.

Exclusion Criteria:

• Pregnant or lactating women, or women who plan to become pregnant within six months;
• Infectious diseases (e.g. HIV, active hepatitis B or C infection, active tuberculosis, etc.);
• GVHD;
• Abnormal vital signs and failure to cooperate with the examination;
• People with mental or mental illness who are unable to cooperate with treatment and efficacy evaluation;
• People with high allergic constitution or severe allergic history, especially those allergic to IL-2;
• Subjects with systemic infection or severe local infection need anti-infection therapy;
• Complicated with dysfunction of heart, lung, brain, liver, kidney and other important organs;
• Any unstable systemic disease: including but not limited to unstable angina pectoris, cerebrovascular accident or transient cerebral ischemia (within 6 months before screening), myocardial infarction (within 6 months before screening), congestive heart failure (NYHA classification =III);
• Doctors believe that there are other reasons for not being included in treatment.

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• B-cell Lymphoma
• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• hCD19.IL15.CAR-iNKT
Universal hCD19.IL15.CAR-iNKT cells by a single infusion intravenously will be given in escalating doses.

Locations

Country	Name	City	State
China	The Affiliated hospital of Xuzhou medical University	Xuzhou	Jiangsu

Sponsors (7)

Lead Sponsor	Collaborator
Kai Lin Xu; Jun Nian Zheng	Affiliated Hospital of Jiangsu University, First Affiliated Hospital of Zhejiang University, Huai 'an First People's Hospital, Nantong University, North Jiangsu People's Hospital, The First People's Hospital of Changzhou

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicity	Adverse events assessed according to NCI-CTCAE v5.0 criteria	Baseline up to 28 days after T cell infusion
Secondary	MRD negative overall response rate (MRD- ORR)	Assessment of MRD negative overall response rate (MRD- ORR) at 3 months of treatment	3 months
Secondary	Overall response rate (ORR)	Assessment of ORR (ORR = CR + CRi ) at Month 6, 12, 18 and 24	Month 6, 12, 18 and 24
Secondary	Event-free survival (EFS)	Assessment of EFS at Month 6, 12, 18 and 24	Month 6, 12, 18 and 24
Secondary	Overall survival (OS)	Assessment of OS at Month 6, 12, 18 and 24	Month 6, 12, 18 and 24