Humanized CD19 Chimeric Antigen Receptor (CAR)-Modified T Cell Therapy in Treating Patients With B-cell Malignancies

NCT ID: NCT04008251

Last Updated: 2019-08-07

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-27
• Study Completion Date: 2022-12-31

Brief Summary

This is a single arm, open-label study to evaluate the safety and efficacy of humanized anti-CD19 CAR-T cells in patients with relapsed or refractory B cell Malignancies.

Detailed Description

Chimeric antigen receptor (CAR)-modified T cells (CAR-T cells) have the capabilities to recognize tumor associated antigen and kill tumor cells specifically. CAR-T therapy showed great effect on patients with relapsed or refractory B cell malignancies. To improve the efficacy and safety, the researchers designed a second-generation humanized CAR, consisting of humanized CD19 single chain variable fragment (scFv) and CD137 costimulatory domain. This study aims to evaluate the safety and effectiveness of humanized anti-CD19 CAR-T cells in patients with relapsed or refractory B cell Malignancies.

Conditions

Acute Lymphoblastic Leukemia; B Cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Second generation humanized CAR-T cells

Patients receive humanized CD19 CAR-T cells transduced with a lentiviral vector on days 0/1/2 in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Second generation humanized CAR-T cells

Intervention Type: GENETIC

Patients receive humanized CD19 CAR-T cells transduced with a lentiviral vector on days 0/1/2 in the absence of disease progression or unacceptable toxicity.

Interventions

Second generation humanized CAR-T cells

Patients receive humanized CD19 CAR-T cells transduced with a lentiviral vector on days 0/1/2 in the absence of disease progression or unacceptable toxicity.

Intervention Type: GENETIC

Eligibility Criteria

Inclusion Criteria

1. The patient is pathologically and histologically confirmed as CD19 + B cell tumors, and has no effective treatment options currently, such as chemotherapy; or relapsed after auto-HSCT/allo-HSCT; or patients voluntarily choose CD19 CAR-T cells as a first treatment;

2. B cell hematological malignancies include the following three categories:

A. B-cell acute lymphocytic leukemia (B-ALL);

B. Indolent B-cell lymphoma (CLL, FL, MZL, LPL);

C. Aggressive B-cell lymphoma (DLBCL, BL, MCL);

3. Aged from 14 to 70 years old;

4. Expected survival time > 6 months;

5. Female patients around childbearing age, negative pregnancy test before trial, and agreed to take effective contraceptive measures during the trial until the last visit;

6. Voluntarily participate in this experiment and sign informed consent by themself, or legally authorized representative.

Exclusion Criteria

1. With a history of epilepsy or other central nervous system diseases;

2. Having graft-versus-host reaction, requires the use of immunosuppressants;

3. The presence of clinically significant cardiovascular disease, such as uncontrolled or symptomatic arrhythmias, congestive heart failure or myocardial infarction within recent six months, or heart disease with cardiac function in any grade 3 (moderate) or 4 ( severe) (according to the New York Heart Association (NYHA) Functional Classification System);

4. Pregnant or lactating women (safety of this therapy for the unborn child is unknown);

5. Not curable active infection;

6. Patients with active hepatitis B or hepatitis C virus infection;

7. Combined use of systemic steroids within two weeks (except use of inhaled steroid recently or currently);

8. Using product of gene therapy before;

9. Creatinine> 2.5 mg / dl (221.0 umol/L); ALT / AST> 3 X the normal amount; Bilirubin> 2.0 mg / dl (34.2 umol/L);

10. Patients suffering from other uncontrolled diseases, and researchers believe that the patient is not suitable for trial;

11. Patients with HIV-infection;

12. Any situation that may increase the risk of patients or interfere with test results.

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

OTHER

Sponsor Role: collaborator

Jingzhou Central Hospital

OTHER

Sponsor Role: collaborator

Xiangyang Central Hospital

OTHER

Sponsor Role: collaborator

People Hospital Of Yichang

UNKNOWN

Sponsor Role: collaborator

Wuhan Sian Medical Technology Co., Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Heng Mei, M.D., Ph.D

Role: PRINCIPAL_INVESTIGATOR

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Locations

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, China

Site Status: RECRUITING

Countries

China

Central Contacts

Yu Hu, M.D., Ph.D

Role: CONTACT

dr_huyu@126.com

86-13986183871

Heng Mei, M.D., Ph.D

Role: CONTACT

hmei@hust.edu.cn

86-13886160811

Facility Contacts

Yu Hu, M.D., Ph.D

Role: primary

dr_huyu@126.com

86-13986183871

Heng Mei, M.D., Ph.D

Role: backup

hmei@hust.edu.cn

86-13886160811

References

Du M, Mayombo RTM, Liu J, Zhang Y, Liao D, Hu Y, Mei H. The impact of obesity and its related underlying diseases on cytokine release syndrome and the efficacy of CAR-T therapy in treating B-cell malignancies. Ann Hematol. 2025 Mar;104(3):1887-1895. doi: 10.1007/s00277-025-06338-6. Epub 2025 Apr 8.

Reference Type: DERIVED

PMID: 40195173 (View on PubMed)

Zhang Y, Zhou F, Wu Z, Li Y, Li C, Du M, Luo W, Kou H, Lu C, Mei H. Timing of Tocilizumab Administration Under the Guidance of IL-6 in CAR-T Therapy for R/R Acute Lymphoblastic Leukemia. Front Immunol. 2022 Jun 21;13:914959. doi: 10.3389/fimmu.2022.914959. eCollection 2022.

Reference Type: DERIVED

PMID: 35799791 (View on PubMed)

Other Identifiers

CART-huCD19-01

Identifier Type: -

Identifier Source: org_study_id