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

Cellular Biomedicine Group

Status and phase

Completed

Phase 1

Conditions

Refractory Diffuse Large B-Cell Lymphoma

Treatments

Biological: C-CAR-011

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT02976857

CBMG2016002

Details and patient eligibility

About

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

Full 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).

Enrollment

15 estimated patients

Sex

All

Ages

18 to 70 years old

Volunteers

No 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