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

Wuhan Sian Medical Technology

Status and phase: Unknown; Phase 1

Conditions: B Cell Lymphoma; Acute Lymphoblastic Leukemia

Treatments: Genetic: Second generation humanized CAR-T cells

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04008251

CART-huCD19-01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 10 estimated patients

Sex: All

Ages: 14 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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10 participants in 1 patient group

Second generation humanized CAR-T cells

Experimental group

Description:

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.

Treatment:

Genetic: Second generation humanized CAR-T cells