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

Primary Purpose

Acute Lymphoblastic Leukemia, B Cell Lymphoma

Status

Unknown status

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

Second generation CAR-T cells

About this trial

This is an interventional treatment trial for Acute Lymphoblastic Leukemia

Eligibility Criteria

undefined - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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;
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);
< 70 years old;
Expected survival time > 6 months;
Female patients around childbearing age, negative pregnancy test before trial, and agreed to take effective contraceptive measures during the trial until the last visit;
Voluntarily participate in this experiment and sign informed consent by themself, or legally authorized representative.

Exclusion Criteria:

With a history of epilepsy or other central nervous system diseases;
Having graft-versus-host reaction, requires the use of immunosuppressants;
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);
Pregnant or lactating women (safety of this therapy for the unborn child is unknown);
Not curable active infection;
Patients with active hepatitis B or hepatitis C virus infection;
Combined use of systemic steroids within two weeks (except use of inhaled steroid recently or currently);
Using product of gene therapy before;
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);
Patients suffering from other uncontrolled diseases, and researchers believe that the patient is not suitable for trial;
Patients with HIV-infection;
Any situation that may increase the risk of patients or interfere with test results.

Sites / Locations

Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Second generation CAR-T cells

Arm 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.

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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).

Overall survival

OS was calculated from the first CAR-T cell infusion to death or last follow-up (censored).

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).

Relapse-free survival

RFS was calculated from the first CAR-T cell infusion to relapse or last visit (censored).

Rate and quantity of anti-CD19 CAR-T cells in bone marrow cells and peripheral blood cells

In vivo (bone marrow and peripheral blood) rate and quantity of CAR-T cells were determined by means of flow cytometry and qPCR.

Full Information

NCT ID

NCT02965092

First Posted

November 13, 2016

Last Updated

May 8, 2019

Sponsor

Wuhan Sian Medical Technology Co., Ltd

Collaborators

Wuhan Union Hospital, China, Jingzhou Central Hospital, Xiangyang Central Hospital, People Hospital Of Yichang

1. Study Identification

Unique Protocol Identification Number

NCT02965092

Brief Title

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 CD19 Chimeric Antigen Receptor (CAR)-Modified T Cells

Study Type

Interventional

2. Study Status

Record Verification Date

May 2019

Overall Recruitment Status

Unknown status

Study Start Date

December 2, 2015 (Actual)

Primary Completion Date

January 2021 (Anticipated)

Study Completion Date

December 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Wuhan Sian Medical Technology Co., Ltd

Collaborators

Wuhan Union Hospital, China, Jingzhou Central Hospital, Xiangyang Central Hospital, People Hospital Of Yichang

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Lymphoblastic Leukemia, B Cell Lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Second generation CAR-T cells

Arm Type

Experimental

Arm 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.

Intervention Type

Genetic

Intervention Name(s)

Second generation CAR-T cells

Other Intervention Name(s)

CAR-T cells

Primary Outcome Measure Information:

Title

Number of participants with adverse events

Description

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)

Time Frame

5 years

Secondary Outcome Measure Information:

Title

One-month remission rate

Description

Response of B-ALL to CAR-T therapy was assessed on day 30 (±2), against the National Comprehensive Cancer Network (NCCN, Version 1.2015).

Time Frame

1 month

Title

Overall survival

Description

OS was calculated from the first CAR-T cell infusion to death or last follow-up (censored).

Time Frame

5 years

Title

Event-free survival

Description

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).

Time Frame

5 years

Title

Relapse-free survival

Description

RFS was calculated from the first CAR-T cell infusion to relapse or last visit (censored).

Time Frame

5 years

Title

Rate and quantity of anti-CD19 CAR-T cells in bone marrow cells and peripheral blood cells

Description

In vivo (bone marrow and peripheral blood) rate and quantity of CAR-T cells were determined by means of flow cytometry and qPCR.

Time Frame

5 years

10. Eligibility

Sex

All

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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; 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); < 70 years old; Expected survival time > 6 months; Female patients around childbearing age, negative pregnancy test before trial, and agreed to take effective contraceptive measures during the trial until the last visit; Voluntarily participate in this experiment and sign informed consent by themself, or legally authorized representative. Exclusion Criteria: With a history of epilepsy or other central nervous system diseases; Having graft-versus-host reaction, requires the use of immunosuppressants; 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); Pregnant or lactating women (safety of this therapy for the unborn child is unknown); Not curable active infection; Patients with active hepatitis B or hepatitis C virus infection; Combined use of systemic steroids within two weeks (except use of inhaled steroid recently or currently); Using product of gene therapy before; 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); Patients suffering from other uncontrolled diseases, and researchers believe that the patient is not suitable for trial; Patients with HIV-infection; Any situation that may increase the risk of patients or interfere with test results.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Yu Hu, M.D., Ph.D

Phone

86-13986183871

dr_huyu@126.com

First Name & Middle Initial & Last Name or Official Title & Degree

Heng Mei, M.D., Ph.D

Phone

86-13886160811

hmei@hust.edu.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yu Hu, M.D., Ph.D

Organizational Affiliation

Wuhan Union Hospital, China

Official's Role

Principal Investigator

Facility Information:

Facility Name

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

City

Wuhan

State/Province

Hubei

ZIP/Postal Code

027

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yu Hu, M.D., Ph.D

Phone

86-13986183871

dr_huyu@126.com

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

35799791

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.

Results Reference

derived

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

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