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

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.

Study Overview

• Status: Recruiting
• Conditions: Refractory Leukemia; Relapse Leukemia
• Intervention / Treatment: Biological: Allogeneic CD19 CAR-T cells

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 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.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518000
      • Recruiting
      • Li Yu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group; Subjects who meet the enrollment conditions will receive intravenous infusion of allogeneic CD19 CAR-T cells after pretreatment.	Biological: Allogeneic CD19 CAR-T cells; infusion of allogeneic CD19 CAR-T cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CRR	Complete remission rate	From data of enrollment until the first documented progression of disease, up to 2 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall survival rate	From admission to the end of follow up, up to 2 years.

Collaborators and Investigators

• Sponsor: Shenzhen University General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2021
• Primary Completion (Anticipated): February 1, 2024
• Study Completion (Anticipated): February 1, 2024

Study Registration Dates

• First Submitted: November 22, 2021
• First Submitted That Met QC Criteria: December 7, 2021
• First Posted (Actual): December 20, 2021

Study Record Updates

• Last Update Posted (Actual): December 20, 2021
• Last Update Submitted That Met QC Criteria: December 7, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
• Other Study ID Numbers: HEM-ONCO-007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No