Safety and Efficacy of CD19 CAR-T/CAR-NK Cells

Head of Hematology，Vice President and Secretary-General of Shandong Stem Cell Society

To investigate the safety and efficacy of CD19 CAR-T/CAR-NK cells in patients with relapsed/refractory B-cell lymphoma and acute B-lymphoblastic leukemia.

Study Overview

• Status: Active, not recruiting
• Conditions: Safety and Efficacy
• Intervention / Treatment: Biological: CAR-T/CAR-NK cells

Detailed Description

Patients who met the exclusion criteria were treated with advanced FC regimen, and subjects who met the infusion criteria assessed by the investigators were given CAR-T/CAR-NK cell infusion 1 to 2 days after completion of eluvial chemotherapy. The CAR-T/CAR-NK dose is calculated according to the patient's body weight, and the total number of cells transfused is about 1-2x106 /kg. Single intravenous infusion.

The study was divided into five stages: screening period, single harvest period, pretreatment chemotherapy period, treatment period, observation and follow-up period after treatment.

For lymphoma, refer to the 2014 version of Lugano efficacy evaluation criteria

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Shandong
    • Shandong, Shandong, China, 250000
      • Shandong Province

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria 1) CD19-positive recurrent, refractory, drug-resistant B-cell lymphoma and acute B-lymphoblastic leukemia. 2) Recurrent MRD-positive refractory acute B lymphoblastic leukemia, extramedullary leukemia lesions. 3) Age over 15 and under 80. 4) KPS≥50 or ECOG score ≤2 and expected survival greater than 3 months. 5) At least 2 weeks prior to apheresis or at least 5 drug half-lives (whichever is shorter) without systemic therapy (except systemic immune checkpoint suppression or activation therapy). 6) The absolute number of neutrophils is greater than 1.5x109 /L. 7) The absolute number of platelets is greater than 50x109 /L. 8) The absolute number of lymphocytes is greater than or equal to 0.15x109 /L. 9) ALT/AST is less than 3 times the normal value. 10) Total bilirubin less than 1.5mg/dl. 11) Creatinine less than 2.5mg/dl, or creatinine clearance ≥60 mL/min/1.73 m2. 12) The ejection fraction of the heart was greater than or equal to 45%, no pericardial effusion was found without echocardiography (ECHO), and electrocardiogram (ECG) was normal. 14) Blood oxygen saturation is greater than or equal to 92% under normal conditions. 15) No central nervous system metastasis was found in patients with central nervous system leukemia and lymphoma (symptoms, signs, imaging, cerebrospinal fluid). 16) Women of childbearing age who had a negative urine pregnancy test before dosing began and agreed to take effective contraception during the trial until the last follow-up visit. 17) Volunteer to participate in this experiment and sign the informed consent.

Exclusion criteria

1. Patients with expected survival of less than 3 months.
2. Clinical findings (symptoms, signs, imaging, cerebrospinal fluid) of central nervous system leukemia.
3. Patients with hyperleukocytoemia (white blood cell count ≥50 x109 /L) or patients whose disease is progressing rapidly at the time of enrollment, as determined by the investigator, to be unable to ensure the completion of a full treatment cycle.
4. Patients with skin cancer other than melanoma or other primary tumors (such as cervical cancer, bladder cancer, breast cancer) (unless cured for more than 3 years).
5. Patients with infections including fungal, bacterial, viral or other uncontrolled infections or those requiring level 4 isolation.
6. Patients who test positive for HIV, HBV, HCV.
7. Patients with central nervous system diseases including stroke, epilepsy, dementia or autoimmune central nervous system diseases.
8. Myocardial infection, cardiac angiography or stenting, active angina pectoris or other obvious clinical symptoms, or cardiac asthma or cardiovascular lymphocyte infiltration in the 12 months prior to enrollment.
9. Those who are receiving anticoagulation therapy or have severe coagulation dysfunction.
10. According to the investigator's judgment, the drug treatment the patient is receiving will affect the safety and efficacy study of this project.
11. Patients with allergy or history of allergy to the biologics used in this project.
12. Pregnant or lactating women.
13. Systematic use of systemic or systemic steroid drugs within 2 weeks prior to treatment (except those who have recently or currently used inhaled steroids).
14. The efficiency of T cell transduction by replication-deficient lentivirus is less than 30%, or the ability to expand in response to CD3 / CD28 costimulatory signals is insufficient (<5 times).
15. Those who have other uncontrolled diseases that the researchers consider unsuitable for enrollment.
16. Any situation that the investigator believes may increase the risk to the subject or interfere with the test results.
17. Patients who are also participating in other clinical studies.

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: experimental group	Biological: CAR-T/CAR-NK cells; One to two days after completion of eluvial chemotherapy, CAR-T/CAR-NK cells were transfused in subjects assessed by the investigators as eligible for infusion. The CAR-T/CAR-NK dose is calculated according to the patient's body weight, and the total number of cells transfused is about 1-2x106 /kg. Single intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	With reference to iRecist1.1, the proportion of patients whose tumor volume shrank to the pre-specified value and maintained the minimum time limit.The time from randomization to tumor progression or death from any cause.	At least half a year
PFS	In tumor therapy, the proportion of patients whose tumor volume has shrunk to a predetermined value and can be maintained for a certain time. It includes the number of patients with complete response (CR) and partial response (PR) as a proportion of the total number of evaluable cases	one year

Collaborators and Investigators

• Sponsor: The Second Hospital of Shandong University

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: August 13, 2024
• First Submitted That Met QC Criteria: September 12, 2024
• First Posted (Estimated): September 19, 2024

Study Record Updates

• Last Update Posted (Estimated): September 19, 2024
• Last Update Submitted That Met QC Criteria: September 12, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: 2024CAR-T/NK B-nhl/ALL

Drug and device information, study documents

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