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 2; Phase 1

Conditions: B Cell Lymphoma; Acute Lymphoblastic Leukemia

Treatments: Genetic: Second generation CAR-T cells

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02965092

CART-CD19-01

Details and patient eligibility

About

This is a single arm, open-label, phase 1/2 study to evaluate the safety and efficacy of 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. CAR consists of single chain variable fragment (scFv) and activation domain of T cell. In preclinical study, the researchers constructed a second generation CAR containing CD137 costimulatory domain. This study aims to evaluate the safety and effectiveness of anti-CD19 CAR-T cells in patients with relapsed or refractory B cell Malignancies.

Enrollment: 80 estimated patients

Sex: All

Ages: Under 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 autologous hematopoietic stem cell transplantation (auto-HSCT); or patients voluntarily choose CD19 CAR-T cells as a first treatment;

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

   • B-cell acute lymphocytic leukemia (B-ALL);
   • Indolent B-cell lymphoma (CLL, FL, MZL, LPL);
   • Aggressive B-cell lymphoma (DLBCL, BL, MCL);

3. < 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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80 participants in 1 patient group

Second generation CAR-T cells

Experimental group

Description:

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

Treatment:

Genetic: Second generation CAR-T cells