Back to results

A Study of Anti-CD19 CAR-T Cell Immunotherapy for Refractory /Relapsed B Cell Malignancies

Primary Purpose

Acute Lymphocytic Leukemia, Chronic Lymphocytic Leukemia, Lymphoma

Status

Unknown status

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

Drugs and anti-CD19 CAR transduced T cells

About this trial

This is an interventional treatment trial for Acute Lymphocytic Leukemia

Eligibility Criteria

14 Years - 80 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients must have a CD19+ B cell malignancy，including relapsed or refractory B cell leukemia and/or B cell lymphoma；
Patients must have a measurable or evaluable disease at the time of enrollment, which may include any evidence of disease including minimal residual disease detected by flow cytometry, cytogenetics, or polymerase chain reaction (PCR) analysis；
Patients with history of allogeneic stem cell transplantation are eligible, providing 6 months had elapsed from SCT, they have no evidence of active graft-versus-host disease (GVHD) and no longer taking immunosuppressive agents during the treatment;
Able to understand and sign the Informed Consent Document；
There is no obvious dysfunctions in heart , liver, lung, kidney, and performance status with ECOG < 2；
Life expectancy：More than 3 months for leukemia and more than 6 months for lymphoma.

Exclusion Criteria:

Patients that require urgent therapy due to tumor mass effects such as bowel obstruction or blood vessel compression；
Patients that have active hemolytic anemia；
Patients who have uncontrollable infectious diseases within 2 weeks before enrollment;
Patients with human immunodeficiency virus (HIV) antibody seropositive;
Active infection of Hepatitis B virus and / or hepatitis C virus;
Patients with any residual intracranial implants；
Coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system；
Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease)；
Concurrent opportunistic infections；
Concurrent systemic steroid therapy；
History of severe immediate hypersensitivity reaction to any of the agents used in this study；
Women of child-bearing potential who are pregnant or breastfeeding；
Patients with cardiac atrial or cardiac ventricular lymphoma involvement；
Other anti-neoplastic investigational agents currently or within 30 days prior to start of the treatment；
Psychiatric patients;
Previous treatment with any gene therapy products.

Sites / Locations

Department of Hematology, Dongguan People's HospitalRecruiting
Department of Hematology, the First People's Hospital of FoshanRecruiting
Department of Hematology, Guangzhou First People's HospitalRecruiting
Department of Hematology, The First Affiliated Hospital of Guangdong Pharmaceutical UniversityRecruiting
Department of Hematology,the Second Affiliated Hospital of Guangzhou Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Anti-CD19 CAR transduced T cells

Arm Description

Patients will receive a lymphodepleting preconditioning regimen with Fludarabine and Cyclophosphamide followed by anti-CD19 CAR-transduced T cells.

Outcomes

Primary Outcome Measures

Number of participants with Adverse Events

To evaluate the safety and feasibility of the administration of anti-CD19 CAR transduced T cells in patients with refractory /relapsed CD19+ B cell malignancies.

Number of participants with clinical responses

To determine if the treatment regimen can result in clinical regression of B cell malignancies in the patients as described above.

Secondary Outcome Measures

Evaluation of overall survial

To evaluate overall survial(OS) after administration of anti-CD19 CAR transduced T cells in patients with refractory /relapsed CD19+ B cell malignancies.

Full Information

NCT ID

NCT03191773

First Posted

June 15, 2017

Last Updated

June 17, 2017

Sponsor

Second Affiliated Hospital of Guangzhou Medical University

Collaborators

Shenzhen Institute for Innovation and Translational Medicine, Guangzhou First People's Hospital, First People's Hospital of Foshan, Dongguan People's Hospital, The First Affiliated Hospital of Guangdong Pharmaceutical University

1. Study Identification

Unique Protocol Identification Number

NCT03191773

Brief Title

A Study of Anti-CD19 CAR-T Cell Immunotherapy for Refractory /Relapsed B Cell Malignancies

Official Title

A Prospective, Multicenter, Single-Arm Study of Anti-CD19 CAR-T Cell Immunotherapy for Refractory /Relapsed B Cell Malignancies

Study Type

Interventional

2. Study Status

Record Verification Date

June 2017

Overall Recruitment Status

Unknown status

Study Start Date

June 30, 2017 (Anticipated)

Primary Completion Date

December 31, 2020 (Anticipated)

Study Completion Date

December 31, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Second Affiliated Hospital of Guangzhou Medical University

Collaborators

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

5. Study Description

Brief Summary

Autologous T cells engineered to express an anti-CD19 chimeric antigen receptor (CAR) will be infused back to patients with refractory /relapsed B cell malignancies, including lymphoma and leukemia. The patients will be monitored after infusion of anti-CD19 CAR-transduced T cells for safety,adverse events, persistence of anti-CD19 CAR-transduced T cells and treatment efficacy.

Detailed Description

Despite progress has been made to date in the treatment of patients with B cell malignancies, including leukemia and lymphoma, many patients with relapsed or refractory diseases do not respond to the standard treatments. It has been shown that anti-CD19 CAR-transduced T cells may be an effective approach to treat the relapsed or refractory diseases. The procedure involves collecting PBMCs from the patients and modifying the T cells to attack the malignant B cells. In this trial, autologous T cells engineered to express an anti-CD19 chimeric antigen receptor (CAR) containing the signaling domains of CD28 or 4-1BB and CD3-zeta will be infused back to patients with B cell malignancies, including lymphoma and leukemia. The patients will be pretreated with a lymphodepleting preconditioning regimen before the infusion of anti-CD19 CAR T cells, and will be monitored for safety, adverse events, persistence of anti-CD19 CAR-transduced T cells and the treatment efficacy.

6. Conditions and Keywords

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

Acute Lymphocytic Leukemia, Chronic Lymphocytic Leukemia, 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

100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Anti-CD19 CAR transduced T cells

Arm Type

Experimental

Arm Description

Patients will receive a lymphodepleting preconditioning regimen with Fludarabine and Cyclophosphamide followed by anti-CD19 CAR-transduced T cells.

Intervention Type

Combination Product

Intervention Name(s)

Drugs and anti-CD19 CAR transduced T cells

Intervention Description

Drug: Fludarabine On days -4 through -2, Fludarabine 30mg/m2 (IV) will be infused over 30 minutes. Drug: Cyclophosphamide On days -4 through -2, Cyclophosphamide 300-500mg/m2 IV will be infused over 60 minutes followed by fludarabine. Biological: Anti-CD19-CAR T cells On day 0, cells will be infused intravenously IV over 20 - 30 minutes.

Primary Outcome Measure Information:

Title

Number of participants with Adverse Events

Description

To evaluate the safety and feasibility of the administration of anti-CD19 CAR transduced T cells in patients with refractory /relapsed CD19+ B cell malignancies.

Time Frame

24 months

Title

Number of participants with clinical responses

Description

To determine if the treatment regimen can result in clinical regression of B cell malignancies in the patients as described above.

Time Frame

24 months

Secondary Outcome Measure Information:

Title

Evaluation of overall survial

Description

To evaluate overall survial(OS) after administration of anti-CD19 CAR transduced T cells in patients with refractory /relapsed CD19+ B cell malignancies.

Time Frame

24 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

14 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients must have a CD19+ B cell malignancy，including relapsed or refractory B cell leukemia and/or B cell lymphoma； Patients must have a measurable or evaluable disease at the time of enrollment, which may include any evidence of disease including minimal residual disease detected by flow cytometry, cytogenetics, or polymerase chain reaction (PCR) analysis； Patients with history of allogeneic stem cell transplantation are eligible, providing 6 months had elapsed from SCT, they have no evidence of active graft-versus-host disease (GVHD) and no longer taking immunosuppressive agents during the treatment; Able to understand and sign the Informed Consent Document； There is no obvious dysfunctions in heart , liver, lung, kidney, and performance status with ECOG < 2； Life expectancy：More than 3 months for leukemia and more than 6 months for lymphoma. Exclusion Criteria: Patients that require urgent therapy due to tumor mass effects such as bowel obstruction or blood vessel compression； Patients that have active hemolytic anemia； Patients who have uncontrollable infectious diseases within 2 weeks before enrollment; Patients with human immunodeficiency virus (HIV) antibody seropositive; Active infection of Hepatitis B virus and / or hepatitis C virus; Patients with any residual intracranial implants； Coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system； Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease)； Concurrent opportunistic infections； Concurrent systemic steroid therapy； History of severe immediate hypersensitivity reaction to any of the agents used in this study； Women of child-bearing potential who are pregnant or breastfeeding； Patients with cardiac atrial or cardiac ventricular lymphoma involvement； Other anti-neoplastic investigational agents currently or within 30 days prior to start of the treatment； Psychiatric patients; Previous treatment with any gene therapy products.

Central Contact Person:

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

Ying Feng, MD

Phone

0086 13602723030

fyzlply@163.com

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

Mingjun Wang, MD

Phone

0086 15814723218

mingjunw429@163.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ying Feng, MD

Organizational Affiliation

Second Affiliated Hospital of Guangzhou Medical University

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Mingjun Wang, MD

Organizational Affiliation

Shenzhen Institute for Innovation and Translational Medicine

Official's Role

Study Director

Facility Information:

Facility Name

Department of Hematology, Dongguan People's Hospital

City

Dongguan

State/Province

Guangdong

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yirong Jiang, MD

Phone

0086 13688967985

dgjyr0769@163.com

First Name & Middle Initial & Last Name & Degree

Yirong Jiang, MD

Facility Name

Department of Hematology, the First People's Hospital of Foshan

City

Foshan

State/Province

Guangdong

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Zhuowen Chen, MD

Phone

0086 18928617712

czwen@fsyyy.com

First Name & Middle Initial & Last Name & Degree

Wei Luo, MD

Phone

0086 18038865996

luowei_421@163.com

First Name & Middle Initial & Last Name & Degree

Zhuowen Chen, MD

Facility Name

Department of Hematology, Guangzhou First People's Hospital

City

Guangzhou

State/Province

Guangdong

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Shunqing Wang

Phone

0086 13437801998

drwangshq@medmail.com.cn

First Name & Middle Initial & Last Name & Degree

Shunqing Wang, MD

Facility Name

Department of Hematology, The First Affiliated Hospital of Guangdong Pharmaceutical University

City

Guangzhou

State/Province

Guangdong

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Xueyi Pan

Phone

0086 13922217835

xypan88@163.com

First Name & Middle Initial & Last Name & Degree

Xueyi Pan, MD

Facility Name

Department of Hematology,the Second Affiliated Hospital of Guangzhou Medical University

City

Guangzhou

State/Province

Guangdong

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ying Feng, MD

Phone

0086 13602723030

fyzlply@163.com

First Name & Middle Initial & Last Name & Degree

Ying Feng, MD

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

A Study of Anti-CD19 CAR-T Cell Immunotherapy for Refractory /Relapsed B Cell Malignancies

We'll reach out to this number within 24 hrs