Allogeneic CD19 CAR-T Cells for the Treatment of Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia

Refractory Leukemia Clinical Trial

— CAR-T  

Official title:

Allogeneic CD19 CAR-T Cells for the Treatment of Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05164042
• Other study ID #: HEM-ONCO-007
• 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
• Phone: +8675521839178
• Email: liyu[@]vip.163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

CD19 CAR-T has been widely developed in patients with R/R ALL and has also been generally recognized by the industry. In 2017, the U.S. FDA approved Novartis's CD 19 CAR-T product Kymriah for the treatment of R/R ALL. 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 derived from healthy donors are not only sufficient in quantity and quality guaranteed, but also available at any time. In December 2020, lancet reported a clinical study of 19 patients receiving allogeneic CAR-T cell ALL. 14 patients were evaluated as CR/CRi (67%) 28 days after treatment, and the median sustained remission time was 4.1 moon. Allogeneic CAR-T cells are safe and effective for the treatment of ALL, and their clinical application range is expected to improve the remission rate and survival rate of patients with R/R ALL.

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 2018, New England Journal published the long-term follow-up data of CD19 CAR-T for relapse/refractory (R/R) ALL, 53 patients with r/r ALL who received a single infusion of CD19 CAR-T The response efficiency (CR+PR) reached 98%, of which about 83% of CR patients, with a median survival time of 12.9 months; greatly improved the remission rate and survival rate of r/r ALL patients.

Nowadays,CD19 CAR-T has been widely developed in patients with R/R ALL and has also been generally recognized by the industry. In 2017, the U.S. FDA approved Novartis's CD CAR-T product Kymriah for the treatment of R/R ALL. 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 derived from healthy donors are not only sufficient in quantity and quality guaranteed, but also available at any time. In December 2020, lancet reported a clinical study of 19 patients receiving allogeneic CAR-T cell ALL. 14 patients were evaluated as CR/CRi (67%) 28 days after treatment, and the median sustained remission time was 4.1 moon. Allogeneic CAR-T cells are safe and effective for the treatment of ALL, and their clinical application range is expected to improve the remission rate and survival rate of patients with R/R ALL.

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 acute lymphoblastic leukemia (r/r B-ALL);

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

4. Expected survival time = 3 months;

5. Flow cytometry confirms that the original 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.

Exclusion Criteria:

1. Primitive 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;

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

• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Refractory Leukemia
• Relapse Leukemia

Intervention

Biological:
• Allogeneic CD19 CAR-T cells
infusion of allogeneic CD19 CAR-T cells

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	CRR	Complete remission rate	From data of enrollment until the first documented progression of disease, up to 2 years.
Secondary	OS	Overall survival rate	From admission to the end of follow up, up to 2 years.