Clinical trial NCT04008251: Humanized CD19 Chimeric Antigen Receptor (CAR)-Modified T Cell Therapy in Treating Patients With B-cell Malignancies
Official title: Treatment of Relapsed or Refractory B-cell Malignancies by Humanized CD19 Chimeric Antigen Receptor (CAR)-Modified T Cells
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Acute Lymphoblastic Leukemia
B Cell Lymphoma
Lead sponsor: Wuhan Sian Medical Technology Co., Ltd
Sponsor class: INDUSTRY
Collaborators: name: Wuhan Union Hospital, China
name: Jingzhou Central Hospital
name: Xiangyang Central Hospital
name: People Hospital Of Yichang
First posted: 2019-07-05
Enrollment: 10
Sex: ALL
Minimum age (years): 14
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of participants with adverse events
timeFrame: 5 years
Secondary outcomes:
measure: One-month remission rate
timeFrame: 1 month
measure: Overall survival
timeFrame: 5 years
measure: Event-free survival
timeFrame: 5 years
measure: Relapse-free survival
timeFrame: 5 years
measure: Rate of anti-CD19 CAR-T cells in bone marrow cells and peripheral blood cells
timeFrame: 5 years
measure: Quantity of anti-CD19 CAR-T cells in bone marrow cells and peripheral blood cells
timeFrame: 5 years
measure: Quantity of anti-CD19 CAR copies in bone marrow cells and peripheral blood cells
timeFrame: 5 years
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
Study officials:
affiliation: Wuhan Union Hospital, China
name: Heng Mei, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.