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A Phase 1 Study Evaluating Safety and Efficacy of C-CAR011 Treatment in DLBCL Subjects (C-CAR011)

Primary Purpose

Refractory Diffuse Large B-Cell Lymphoma

Status

Completed

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

C-CAR-011

About this trial

This is an interventional treatment trial for Refractory Diffuse Large B-Cell Lymphoma focused on measuring refractory diffuse large B-cell lymphoma, anti-CD19 chimeric antigen receptor T-cell

Eligibility Criteria

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

Inclusion Criteria:

Histologically diagnosed as DLBCL according to the NCCN non-Hodgkin's lymphoma Clinical Practice Guidelines (3rd edition 2016)
Refractory DLBCL
All subjects must have received adequate prior therapy including anti-CD20 monoclonal antibody (unless tumor is CD20-negative) and an anthracycline containing chemotherapy regimen. The standardized treatment regimens reference to NCCN non-Hodgkin lymphoma Clinical Practice Guidelines (2016 Version 3)
At least one measurable lesion per revised IWG Response Criteria (the longest diameter of the tumor ≥ 1.5 cm)
Age 18-70 years old, male or female
Expected survival ≥ 12 weeks
ECOG score 0-1
Subject's left ventricular ejection fraction (LVEF) is ≥ 50% and no evidence of pericardial effusion as determined by an ECHO
At least 4 weeks from receiving previous treatment (radiotherapy, chemotherapy, monoclonal antibody therapy or other treatments)
No contraindications of peripheral blood apheresis
Female subjects in childbearing age, their serum or urine pregnancy test must be negative, and must agree to take effective contraceptive measures during the trial measures
Volunteered to participate in this study and signed informed consent

Exclusion Criteria:

Have a history of allergy to cellular products
Used any genetically modified T cell therapy
History of allogeneic hematopoietic stem cell transplantation
Severe active infection (uncomplicated urinary tract infections, bacterial pharyngitis allowed) or currently receiving intravenous antibiotic therapy and received intravenous antibiotic therapy within one week. Prophylactic antibiotic, antiviral and antifungal treatment is permissible
Hepatitis B or hepatitis C virus infection (including carriers), as well as acquired, congenital immune deficiency diseases, including but not limited to HIV-infected persons
Patients with class III and IV heart failure according to the NYHA Heart Failure Classifications
A history of QT prolongation
A history of epilepsy or other central nervous system disorders
The patient had a history of other primary cancers, with the following exceptions: Excisional non-melanoma such as cutaneous basal cell carcinoma; Cured in situ carcinoma such as cervical cancer, bladder cancer or breast cancer
Subjects with any autoimmune disease or any immune deficiency disease or other disease in need of immunosuppressive therapy
Used of systemic steroids within two weeks (using inhaled steroids is an exception)
Women who are pregnant or lactating or have breeding intent in 6 months
Participated in any other clinical trial within three months
The investigators believe that any increase in the risk of the subject or interference with the results of the trial

Sites / Locations

Hematological Department, People's Hospital of Jiangsu Province

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

C-CAR011

Arm Description

C-CAR011 infusion In the first cell therapy 0, 1 and 2 days, respectively 10%, 30% and 60% ratio three times reinfusion.

Outcomes

Primary Outcome Measures

Dose-limiting toxicity (DLT)

Non-haematological dose-limiting toxicities was any toxicity of grade 3 or higher occurring within 28 days of C-CAR011 infusion judged possibly related to the treatment regimen.The following toxicities were not considered dose limiting toxicities: tumor lysis syndrome, abnormal electrolytes responding to supplementation, hypoalbuminemia, liver dysfunction resolving to ≤grade 2 within 14 days, transient (<72 hours) grade 4 hepatic enzyme abnormality, and grade 3 or 4 fever or neutropenic fever.

Secondary Outcome Measures

Overall response rate

Overall response rate (ORR) = complete response (CR) rate + partial response (PR) rate, ORR will be assessed at weeks 4 and weeks 12 according to International Working Group (IWG) revised criteria.

Disease control rate

Disease control rate (DCR） = complete response (CR) rate + partial response (PR) rate + stable disease (SD) rate, DCR will be assessed at weeks 12 according to International Working Group (IWG) revised criteria.

Full Information

NCT ID

NCT02976857

First Posted

November 21, 2016

Last Updated

January 16, 2019

Sponsor

Cellular Biomedicine Group Ltd.

Collaborators

The First Affiliated Hospital with Nanjing Medical University

1. Study Identification

Unique Protocol Identification Number

NCT02976857

Brief Title

A Phase 1 Study Evaluating Safety and Efficacy of C-CAR011 Treatment in DLBCL Subjects

Acronym

C-CAR011

Official Title

A Phase 1 Single Center, Non-randomized Study Evaluating Safety and Efficacy of Anti-CD19 Chimeric Antigen Receptor T-cell (C-CAR011) Treatment in Subjects With Refractory Diffuse Large B-cell Lymphoma

Study Type

Interventional

2. Study Status

Record Verification Date

November 2016

Overall Recruitment Status

Completed

Study Start Date

December 2016 (undefined)

Primary Completion Date

September 11, 2018 (Actual)

Study Completion Date

January 9, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Cellular Biomedicine Group Ltd.

Collaborators

The First Affiliated Hospital with Nanjing Medical University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The trial is a single arm, single-center, non-randomized phase I clinical trial which is designed to evaluate the safety and efficacy of C-CAR011 in treatment of refractory DLBCL

Detailed Description

The 3x3 dose escalation design will be adopted in order to determine the maximum tolerated dose (MTD). Subjects will be enrolled into low-dose group, medium-dose group and high-dose group as below: Dose CAR+ cells/kg Low 0.8×106 Medium 2.5×106 High 5.0×106 DLT is evaluated within 30 days post C-CAR011 infusion).

6. Conditions and Keywords

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

Refractory Diffuse Large B-Cell Lymphoma

Keywords

refractory diffuse large B-cell lymphoma, anti-CD19 chimeric antigen receptor T-cell

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

15 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

C-CAR011

Arm Type

Experimental

Arm Description

C-CAR011 infusion In the first cell therapy 0, 1 and 2 days, respectively 10%, 30% and 60% ratio three times reinfusion.

Intervention Type

Biological

Intervention Name(s)

C-CAR-011

Other Intervention Name(s)

CAR-CD19

Intervention Description

lymphocytes will be transduced with lentiviral vector containing CAR-CD19 gene.

Primary Outcome Measure Information:

Title

Dose-limiting toxicity (DLT)

Description

Time Frame

28 days

Secondary Outcome Measure Information:

Title

Overall response rate

Description

Overall response rate (ORR) = complete response (CR) rate + partial response (PR) rate, ORR will be assessed at weeks 4 and weeks 12 according to International Working Group (IWG) revised criteria.

Time Frame

4 and 12 weeks

Title

Disease control rate

Description

Time Frame

12 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Histologically diagnosed as DLBCL according to the NCCN non-Hodgkin's lymphoma Clinical Practice Guidelines (3rd edition 2016) Refractory DLBCL All subjects must have received adequate prior therapy including anti-CD20 monoclonal antibody (unless tumor is CD20-negative) and an anthracycline containing chemotherapy regimen. The standardized treatment regimens reference to NCCN non-Hodgkin lymphoma Clinical Practice Guidelines (2016 Version 3) At least one measurable lesion per revised IWG Response Criteria (the longest diameter of the tumor ≥ 1.5 cm) Age 18-70 years old, male or female Expected survival ≥ 12 weeks ECOG score 0-1 Subject's left ventricular ejection fraction (LVEF) is ≥ 50% and no evidence of pericardial effusion as determined by an ECHO At least 4 weeks from receiving previous treatment (radiotherapy, chemotherapy, monoclonal antibody therapy or other treatments) No contraindications of peripheral blood apheresis Female subjects in childbearing age, their serum or urine pregnancy test must be negative, and must agree to take effective contraceptive measures during the trial measures Volunteered to participate in this study and signed informed consent Exclusion Criteria: Have a history of allergy to cellular products Used any genetically modified T cell therapy History of allogeneic hematopoietic stem cell transplantation Severe active infection (uncomplicated urinary tract infections, bacterial pharyngitis allowed) or currently receiving intravenous antibiotic therapy and received intravenous antibiotic therapy within one week. Prophylactic antibiotic, antiviral and antifungal treatment is permissible Hepatitis B or hepatitis C virus infection (including carriers), as well as acquired, congenital immune deficiency diseases, including but not limited to HIV-infected persons Patients with class III and IV heart failure according to the NYHA Heart Failure Classifications A history of QT prolongation A history of epilepsy or other central nervous system disorders The patient had a history of other primary cancers, with the following exceptions: Excisional non-melanoma such as cutaneous basal cell carcinoma; Cured in situ carcinoma such as cervical cancer, bladder cancer or breast cancer Subjects with any autoimmune disease or any immune deficiency disease or other disease in need of immunosuppressive therapy Used of systemic steroids within two weeks (using inhaled steroids is an exception) Women who are pregnant or lactating or have breeding intent in 6 months Participated in any other clinical trial within three months The investigators believe that any increase in the risk of the subject or interference with the results of the trial

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jianyong Li

Organizational Affiliation

The First Affiliated Hospital with Nanjing Medical University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Hematological Department, People's Hospital of Jiangsu Province

City

Nanjing City

State/Province

Jiangsu

ZIP/Postal Code

210029

Country

China

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

34515338

Citation

Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.

Results Reference

derived

Learn more about this trial

A Phase 1 Study Evaluating Safety and Efficacy of C-CAR011 Treatment in DLBCL Subjects

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