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

NCT ID: NCT02976857

Last Updated: 2019-01-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-31
• Study Completion Date: 2019-01-09

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).

Conditions

Refractory Diffuse Large B-Cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

C-CAR011

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

Group Type: EXPERIMENTAL

C-CAR-011

Intervention Type: BIOLOGICAL

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

Interventions

C-CAR-011

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

Intervention Type: BIOLOGICAL

Other Intervention Names

CAR-CD19

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Affiliated Hospital with Nanjing Medical University

OTHER

Sponsor Role: collaborator

Shanghai AbelZeta Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jianyong Li

Role: PRINCIPAL_INVESTIGATOR

The First Affiliated Hospital with Nanjing Medical University

Locations

Hematological Department, People's Hospital of Jiangsu Province

Nanjing, Jiangsu, China

Countries

China

References

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.

Reference Type: DERIVED

PMID: 34515338 (View on PubMed)

Other Identifiers

CBMG2016002

Identifier Type: -

Identifier Source: org_study_id