Clinical trial NCT05143112: Allogeneic CD19 CAR-T Cells for the Treatment of Relapsed/Refractory B-cell Lymphoma
Official title: Allogeneic CD19 CAR-T Cells for the Treatment of Relapsed/Refractory B-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Non-hodgkin Lymphoma,B Cell
Lead sponsor: Shenzhen University General Hospital
Sponsor class: OTHER
First posted: 2021-12-03
Enrollment: 20
Sex: ALL
Minimum age (years): 14
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall response rate
timeFrame: From date of initial treatment to the end of follow up, up to 2 years
Secondary outcomes:
measure: overall survival rate
timeFrame: From admission to the end of follow up, up to 2 years
Other outcomes:
Locations:
city: Shenzhen
country: China
facility: Li Yu
state: Guangdong
Study officials:
affiliation: Shenzhen University General Hospital
name: Li Yu, Dr
role: PRINCIPAL_INVESTIGATOR
References: