Clinical Study of CAR-T Technology for the Treatment of Relapsed Refractory Malignant Haematological Tumours

The trial is designed as an early exploratory single-centre, open, single-arm clinical trial. The trial is planned to evaluate the safety and efficacy of CAR-T for the treatment of relapsed refractory malignant haematological tumours. The trial is divided into five visit periods as follows: screening period, non-myeloablative pretreatment, short-term follow-up period, mid-term follow-up period and exit visit.

Study Overview

• Status: Recruiting
• Conditions: Hematological Malignancy
• Intervention / Treatment: Drug: CAR-T cell therapy

Detailed Description

1) Screening period (-21 to -7 days, 2 weeks): subjects signed the informed consent form and completed a series of examinations, and it was judged by the investigator whether subjects met the inclusion criteria and did not meet the exclusion criteria based on the results of the examinations and the inclusion/exclusion criteria. And the investigator will judge whether some of the examination results within one month before the date of informed consent are acceptable according to the patient's condition.

2) Non-myeloablative preconditioning (-4 to -1 days for 4 days): the need for preconditioning and the preconditioning regimen were decided based on the subject's condition, and the most commonly used regimen was the FC regimen. After returning to the study centre for admission at the time notified by the investigator, subjects received fludarabine and cyclophosphamide on days -4 to -2 of the trial; the drugs were discontinued for 1 day on day -1 and a series of tests were completed as baseline information for subjects after non-clear myeloid preconditioning;

3) Short-term follow-up period (visits 4 to 10: 0 to 180 days over a period of 6 months): subjects return to the study centre for a series of examinations every month for 6 months following the start of infusing back the expected dose of CAR-T cells on Day 0 of the trial. The investigator evaluates the short-term safety and efficacy of CAR-T therapy based on the subjects' examination results;

4) Medium- to long-term follow-up period (180 to 360 days over a period of 6 months): subjects will return to the research centre every 2 months for a series of examinations within 6 months after completion of the short-term follow-up. The investigators will evaluate the mid- and long-term safety and efficacy of CAR-T therapy based on the subjects' examination results;

5) Withdrawal Visit (at any time): all subjects may withdraw from this study at any stage of the trial, with or without providing a reason. If the subject withdraws from the study after the return of the CAR-T cells, he/she will be required to complete the examination items required for the withdrawal visit in the visit flowchart; if the subject withdraws from the visit prior to the return of the CAR-T cells, he/she will be required to complete the safety examination items only, and the reason for the subject's withdrawal will be recorded in detail by the investigator. If the subject stops treatment due to AE, the investigator will follow the subject for necessary safety visits until the subject's AE returns to baseline levels or reaches steady state.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Liangming Ma; Phone Number: 13513629908; Email: maliangming620928@163.com
• Study Contact Backup: Name: Xiaomin Zhang; Phone Number: 13513629908; Email: sxdyyky@126.com

Study Locations

• China
  • Shanxi
    • Taiyuan, Shanxi, China, 030032
      • Recruiting
      • ShanxiBethuneH
      • Contact: Liangming Ma; Phone Number: 13513629908; Email: maliangming620928@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. patients or their legal guardians voluntarily participate and sign an informed consent form;
2. male or female patients aged 14 to 70 years (inclusive);
3. be diagnosed as malignant haematological tumour by pathological and histological examination;
4. have a measurable or evaluable lesion;
5. the patient has good function of major tissues and organs:

(1) Liver function: ALT/AST <3 times upper limit of normal (ULN) and total bilirubin ≤34.2 μmol/L; (2) Renal function: creatinine <220 μmol/L; (3) Lung function: room oxygen saturation ≥95%; (4) Cardiac function: left ventricular ejection fraction (LVEF) ≥40%. (6) Patient's peripheral superficial venous blood flow is smooth and can meet the demand of intravenous drip; 7. patients with ECOG score ≤2 and expected survival time ≥3 months.

Exclusion Criteria:

1. Women who are pregnant (positive urine/blood pregnancy test) or breastfeeding;
2. men or women who are planning to conceive within the last 1 year;
3. patients who cannot guarantee effective contraception (condoms or birth control pills, etc.) within 1 year of enrolment;
4. patients with uncontrolled infections within 4 weeks prior to enrolment;
5. active viral hepatitis B/C;
6. patients with HIV infection;
7. patients with severe autoimmune diseases or immunodeficiency diseases;
8. patients who are allergic to large molecule biopharmaceuticals such as antibodies or cytokines;
9. patients who have participated in other clinical trials within 6 weeks prior to enrolment;
10. the patient has used hormones systematically within 4 weeks prior to enrolment (except for patients using inhaled hormones);
11. the patient has a psychiatric disorder
12. the patient has substance abuse/addiction;
13. other conditions that, in the judgement of the investigator, make the patient unsuitable for enrolment.

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: CAR-T cell therapy; Dose climbing started with 1.0*10^6/kg back infusion, 3 patients per dose group, if there is no adverse reaction the dose can be increased to 2.0*10^6/kg, 4.0*10^6/kg, the maximum dose can be extended the study.

Drug: CAR-T cell therapy; The application of CAR-T therapy in the clinic generally involves the in vitro preparation and in vivo infusion of CAR-T, and the specific experimental process is divided into five steps: (1) isolation of T cells from the peripheral blood of the cancer subjects or single harvested single nucleated cells; (2) use of genetic engineering to transfer CAR structural genes that can specifically recognise the tumour cells into the T cells; (3) in vitro cultivation and expansion of CAR-T cells to the desired infusion dose (4) Non-myeloablative chemotherapy is administered prior to the infusion of CAR-T cells, which is used to remove immunosuppressive cells and reduce the tumour load so as to enhance the efficacy of the treatment; (5) CAR-T cells are infused according to the expected dosage, and the efficacy of the treatment is observed and the adverse reactions are closely monitored.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-related adverse events	Adverse events associated with CAR-T therapy, serious adverse events and clinically significant laboratory test abnormalities.	Up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CAR-T amplification levels	Characterisation of CAR-T cell expansion levels in subjects (peripheral blood, bone marrow, cerebrospinal fluid and lymph nodes, etc.) over time.	Up to 36 months
Duration of the CAR-T	Duration of CAR-T cell persistence in subjects (peripheral blood, bone marrow, cerebrospinal fluid and lymph nodes, etc.	Up to 36 months
Lymphocyte abatement	The characteristics of lymphocyte ablation in the subject.	Up to 36 months
Objective Response Rate (ORR)	Proportion of patients whose tumour volume shrinks to a pre-specified value and who are able to maintain the minimum timeframe required, as the sum of the proportions in complete and partial remission. Objective tumour remission rates at 3 months, 6 months and 1 year follow-up after treatment.It is the sum of the proportions of complete remission (CR) and partial remission (PR).	Up to 6 months
Progression-free survival(PFS)	Time from start of patient's treatment to disease progression or death from any cause	Up to 36 months
Event free survival (EFS)	Time from the start of enrolment to the occurrence of any event.	Up to 36 months

Collaborators and Investigators

• Sponsor: Shanxi Bethune Hospital
• Investigators: Principal Investigator: Xiaomin Zhang, Shanxi Bethune Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2020
• Primary Completion (Estimated): November 15, 2025
• Study Completion (Estimated): December 20, 2025

Study Registration Dates

• First Submitted: January 15, 2024
• First Submitted That Met QC Criteria: January 25, 2024
• First Posted (Actual): February 2, 2024

Study Record Updates

• Last Update Posted (Actual): February 2, 2024
• Last Update Submitted That Met QC Criteria: January 25, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Hematologic Diseases; Hematologic Neoplasms
• Other Study ID Numbers: YXLL-2019-114

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