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

Phase 1

• Conditions: Acute Lymphoblastic Leukemia; B Cell Lymphoma
• Interventions: Genetic: Second generation humanized CAR-T cells

• Registration Number: NCT04008251
• Lead Sponsor: Wuhan Sian Medical Technology Co., Ltd

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.

Study Timeline

• Study Start: 2019-05-27
• Status Verified: 2019-07
• Study First Submitted: 2019-07-01
• Study First Submitted QC: 2019-07-02
• Study First Posted: 2019-07-05
• Last Update Submitted: 2019-08-05
• Last Update Posted: 2019-08-07
• Primary Completion: 2022-07-01
• Study Completion: 2022-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 10

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Second generation humanized CAR-T cells	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.

Primary Outcome Measures

Name	Time	Method
Number of participants with adverse events	5 years	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)

Secondary Outcome Measures

Name	Time	Method
Quantity of anti-CD19 CAR copies in bone marrow cells and peripheral blood cells	5 years	In vivo (bone marrow and peripheral blood) quantity of anti-CD19 CAR copies were determined by means of qPCR.
Overall survival	5 years	OS was calculated from the first CAR-T cell infusion to death or last follow-up (censored).
Rate of anti-CD19 CAR-T cells in bone marrow cells and peripheral blood cells	5 years	In vivo (bone marrow and peripheral blood) rate of CAR-T cells were determined by means of flow cytometry.
One-month remission rate	1 month	Response of B-ALL to CAR-T therapy was assessed on day 30 (±2), against the National Comprehensive Cancer Network (NCCN, Version 1.2015).
Event-free survival	5 years	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).
Relapse-free survival	5 years	RFS was calculated from the first CAR-T cell infusion to relapse or last visit (censored).
Quantity of anti-CD19 CAR-T cells in bone marrow cells and peripheral blood cells	5 years	In vivo (bone marrow and peripheral blood) quantity of CAR-T cells were determined by means of flow cytometry.

Trial Locations

Locations (1)

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; 🇨🇳 Wuhan, Hubei, China