Humanized CAR-T Therapy for Treatment of B Cell Malignancy

Phase 1

• Conditions: Leukemia, Lymphocytic, Chronic, B-Cell
• Interventions: Biological: CAR-T

• Registration Number: NCT02782351
• Lead Sponsor: Kai Lin Xu; Jun Nian Zheng

Brief Summary

The present study evaluates the safety and efficacy of humanized Chimeric antigen receptor T cells (CAR-T) in treating recurrent or refractory B cell malignancy targeting CD19 with a humanized scFv. All participants will receive autologous chimeric antigen receptor engineered T cells.

Detailed Description

CD19 has been extensively evaluated as a therapeutic target for recurrent or refractory B cell malignancy by chimeric antigen receptor T cell therapy, the single chain antibody sequence (scFv) against CD19 derived from a mouse hybridoma was widely employed. However, the immunogenicity of the mouse scFv sequence might be one of the reasons that CAR-T cells cannot persist in vivo for long. In present study investigators replace the mouse-derived scFv with a a humanized one and evaluate its safety and efficacy.

Study Timeline

• Study Start: 2016-05
• Study First Submitted: 2016-05-17
• Study First Submitted QC: 2016-05-22
• Study First Posted: 2016-05-25
• Status Verified: 2017-08
• Last Update Submitted: 2017-08-03
• Last Update Posted: 2017-08-04
• Primary Completion: 2018-06
• Study Completion: 2018-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• Age≥3 at the time of consent
• Survival time>12 weeks
• B cell hematological malignancies by pathological examination
• Chemotherapy failure or recurrent B cell malignancy
• Creatinine< 2.5mg/dl
• Glutamic-pyruvic transaminase, glutamic oxalacetic transaminase< 3 fold of normal level
• Karnofsky Performance Status>50% at the time of screening
• Bilirubin<2.0mg/dl
• Adequate pulmonary, renal, hepatic, and cardiac function
• Fail in autologous or allogenic haemopoietic stem cell transplantation
• Free of leukocytes removal contraindications

Exclusion Criteria

• Pregnant or nursing women
• Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of screening
• Previous treatment with any gene therapy product
• Abnormal vital signs
• Highly allergic constitution or history of severe allergies, especially allergy to interleukin-2
• General infection or local severe infection, or other infection that is not controlled
• Dysfunction in lung, heart, kidney and brain.
• Severe autoimmune diseases
• other symptoms that are not applicable for CAR-T

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CAR-T	CAR-T	In interventional studies, patients enrolled will receive autologous 2nd generation CAR-T cells, which contain a humanized single chain antibody sequence against CD19.

Primary Outcome Measures

Name	Time	Method
CAR-T cells persistence in peripheral blood	12 months	The presence of CAR T cells in patients' peripheral blood will be quantified with real time qPCR

Secondary Outcome Measures

Name	Time	Method
B cell number and immunoglobulins in peripheral blood	12 months	The number of B cells and immunoglobulins in peripheral blood will be evaluated by routine methods

Trial Locations

Locations (2)

Affiliated hospital of Xuzhou medical college; 🇨🇳 Xuzhou, Jiangsu, China

Huaian First People's Hospital; 🇨🇳 Huai'an, Jiangsu, China