Allogeneic CD19 CAR-T Cells for the Treatment of Relapsed/Refractory B-cell Lymphoma

Non-hodgkin Lymphoma,B Cell Clinical Trial

— CAR-T  

Official title:

Allogeneic CD19 CAR-T Cells for the Treatment of Relapsed/Refractory B-cell Lymphoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05143112
• Other study ID #: HEM-ONCO-008
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 5, 2021
• Est. completion date: February 2024

Study information

• Verified date: February 2021
• Source: Shenzhen University General Hospital
• Contact: Li Yu, Dr
• Phone: +8675521839178
• Email: liyu[@]vip.163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Preclinical and clinical studies of CD19 CAR-T in r/r B-NHL have been extensively carried out. At the beginning of 2020, MorphoSys submitted its company-targeted CD19 monoclonal antibody to the FDA for r/r DLBL treatment and obtained FDA priority approval. It further confirms the safety and effectiveness of CD19 as a therapeutic target in r/r B-NHL. However, these CAR-T cells are constructed from patients' autologous T cells, and the production and preparation time is long; on the other hand, most patients have received multiple chemotherapy before CAR-T treatment, and the quantity and quality of T cells often cannot meet the needs of clinical treatment. It is also an important factor leading to the failure of CAR-T cell therapy, which limits the large-scale clinical application of CAR-T.

T cells sourced from healthy people are not only sufficient in quantity and quality guaranteed, but also available at any time. In December 2020, lancet[2] reported a clinical study of 19 patients receiving allogeneic CAR-T cell therapy for B-ALL. 14 patients were evaluated as CR/CRi (67%) 28 days after treatment, with a median sustained remission Time 4.1 months. Allogeneic CAR-T cells are safe and effective for the treatment of B-cell malignant diseases, and their clinical application range is expected to further improve the remission rate and survival rate of patients with R/R B-cell non-Hodgkin's lymphoma.

Description:

Chimeric antigen receptor (CAR) T cells enable T cells to recognize and kill tumor cells that express specific antigens through genetic engineering. CD19 is expressed on the membrane surface of pre-B cells and mature B cells, but not on the surface of T cells and normal granulocytes. It is an ideal therapeutic target for B cell-derived tumors. A large number of previous studies have confirmed that CD19 CAR-T cells are a safe and effective method for the treatment of ALL. In 2019, Locke FL[1] et al. reported a clinical study of CD19 CAR-T for r/r DLBL. 119 patients were enrolled. The objective response rate was 83%, the CR rate was 58%, and the median progression-free survival was 5.9. Months. Greatly improved the patient's prognosis.

Preclinical and clinical studies of CD19 CAR-T in r/r B-NHL have been extensively carried out. At the beginning of 2020, MorphoSys submitted its company-targeted CD19 monoclonal antibody to the FDA for r/r DLBL treatment and obtained FDA priority approval. It further confirms the safety and effectiveness of CD19 as a therapeutic target in r/r B-NHL. However, these CAR-T cells are constructed from patients' autologous T cells, and the production and preparation time is long; on the other hand, most patients have received multiple chemotherapy before CAR-T treatment, and the quantity and quality of T cells often cannot meet the needs of clinical treatment. It is also an important factor leading to the failure of CAR-T cell therapy, which limits the large-scale clinical application of CAR-T.

T cells sourced from healthy people are not only sufficient in quantity and quality guaranteed, but also available at any time. In December 2020, lancet[2] reported a clinical study of 19 patients receiving allogeneic CAR-T cell therapy for B-ALL. 14 patients were evaluated as CR/CRi (67%) 28 days after treatment, with a median sustained remission Time 4.1 months. Allogeneic CAR-T cells are safe and effective for the treatment of B-cell malignant diseases, and their clinical application range is expected to further improve the remission rate and survival rate of patients with R/R B-cell non-Hodgkin's lymphoma.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: February 2024
• Est. primary completion date: February 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 70 Years

Eligibility

Inclusion Criteria:

1. 14-70 years old (including 14, 70 years old), no gender limit;

2. According to the 2020 World Health Organization (WHO) diagnostic criteria, it is diagnosed as relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL);

3. The ECOG behavior status score is 0-2 points;

4. Expected survival time = 3 months;

5. Tumor cells express CD19;

6. Those who have failed autologous CAR-T cell preparation or autologous CAR-T cell therapy under the existing technical conditions;

7. No serious heart, lung, liver, or kidney disease;

8. Ability to understand and willing to sign the informed consent form for this trial.

Cell donors must meet the following criteria to participate in this study:

1. 18-60 years old, no gender limit;

2. A fully matched/half-matched donor with the patient's HLA match;

9) No contraindications to peripheral blood apheresis

Exclusion Criteria:

1. Tumor cells do not express CD19;

2. Active infection;

3. Abnormal liver function (total bilirubin>1.5×ULN, ALT>2.5×ULN), abnormal renal function (serum creatinine>1.5×ULN);

4. People with unstable angina or New York Heart Association class 3/4 congestive heart failure, multiple organ dysfunction;

5. HIV/AIDS patients;

6. Those who need long-term anticoagulation (warfarin or heparin), antiplatelet (aspirin, dose>300mg/d; clopidogrel, dose>75mg/d) treatment;

7. Those who received radiotherapy within 4 weeks before the start of the study (blood sampling);

8. Known or suspected drug abuse or alcohol dependence;

9. People with mental illness or other conditions cannot obtain informed consent, and cannot cooperate with the requirements of completing the experimental treatment and inspection procedures;

10. Participated in other clinical trials within 30 days;

11. Pregnant or lactating women, male subjects (or their partners) or female subjects have a pregnancy plan during the study period to 6 months after the end of the test, and are unwilling to use a medically approved effective contraceptive measure during the test period (Such as intrauterine contraceptive devices or condoms);

12. Those who are judged by the investigator to be unsuitable to participate in this trial

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Non-hodgkin Lymphoma,B Cell

Intervention

Biological:
• Allogeneic CD19 CR-T cell
Allogeneic CD19 CR-T cell infusion

Locations

Country	Name	City	State
China	Li Yu	Shenzhen	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Shenzhen University General Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate	Percentage of patients in complete remission in total treated patients	From date of initial treatment to the end of follow up, up to 2 years
Secondary	overall survival rate	Time from initiation of trial treatment to death	From admission to the end of follow up, up to 2 years