Humanized CAR-T Therapy for Treatment of B Cell Malignancy

Kai Lin Xu; Jun Nian Zheng

Status and phase: Unknown; Phase 2; Phase 1

Conditions: Leukemia, Lymphocytic, Chronic, B-Cell

Treatments: Biological: CAR-T

Study type: Interventional

Funder types: Other

Identifiers

NCT02782351

XYFY2016-KL002-01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 50 estimated patients

Sex: All

Ages: 3+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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50 participants in 1 patient group

CAR-T

Experimental group

Description:

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

Treatment:

Biological: CAR-T