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

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

Treatment of Relapsed or Refractory B-cell Malignancies by Humanized CD19 Chimeric Antigen Receptor (CAR)-Modified T Cells

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04008251
• Other study ID #: CART-huCD19-01
• Status: Recruiting
• Phase: Phase 1
• Start date: May 27, 2019
• Est. completion date: December 31, 2022

Study information

• Verified date: July 2019
• Source: Wuhan Sian Medical Technology Co., Ltd
• Contact: Yu Hu, M.D., Ph.D
• Phone: 86-13986183871
• Email: dr_huyu[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: December 31, 2022
• Est. primary completion date: July 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• B Cell Lymphoma
• Leukemia, Lymphoid
• Lymphoma, B-Cell
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Genetic:
• 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.

Locations

Country	Name	City	State
China	Union Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei

Sponsors (5)

Lead Sponsor	Collaborator
Wuhan Sian Medical Technology Co., Ltd	Jingzhou Central Hospital, People Hospital Of Yichang, Wuhan Union Hospital, China, Xiangyang Central Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with adverse events	Therapy-related adverse events were recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0)	5 years
Secondary	One-month remission rate	Response of B-ALL to CAR-T therapy was assessed on day 30 (±2), against the National Comprehensive Cancer Network (NCCN, Version 1.2015).	1 month
Secondary	Overall survival	OS was calculated from the first CAR-T cell infusion to death or last follow-up (censored).	5 years
Secondary	Event-free survival	EFS was calculated from the first CAR-T cell infusion to death, progression of the disease, relapse or gene recurrence, whichever came first, or last visit (censored).	5 years
Secondary	Relapse-free survival	RFS was calculated from the first CAR-T cell infusion to relapse or last visit (censored).	5 years
Secondary	Rate of anti-CD19 CAR-T cells in bone marrow cells and peripheral blood cells	In vivo (bone marrow and peripheral blood) rate of CAR-T cells were determined by means of flow cytometry.	5 years
Secondary	Quantity of anti-CD19 CAR-T cells in bone marrow cells and peripheral blood cells	In vivo (bone marrow and peripheral blood) quantity of CAR-T cells were determined by means of flow cytometry.	5 years
Secondary	Quantity of anti-CD19 CAR copies in bone marrow cells and peripheral blood cells	In vivo (bone marrow and peripheral blood) quantity of anti-CD19 CAR copies were determined by means of qPCR.	5 years