Humanized CAR-T Therapy for Treatment of B Cell Malignancy

Leukemia, Lymphocytic, Chronic, B-Cell Clinical Trial

Official title:

Humanized CAR-T Therapy for Treatment of Recurrent or Refractory B Cell Malignancy by Targeting CD19

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02782351
• Other study ID #: XYFY2016-KL002-01
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: May 17, 2016
• Last updated: August 3, 2017
• Start date: May 2016
• Est. completion date: December 2018

Study information

• Verified date: August 2017
• Source: Xuzhou Medical University
• Contact: Jiang Cao, M.D., Ph.D.
• Phone: 8651685802291
• Email: zimu05067[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 2018
• Est. primary completion date: June 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Biological:
• CAR-T
Patients will be infused with autologous CAR-T infusion in a dose escalating manner.

Locations

Country	Name	City	State
China	Huaian First People's Hospital	Huai'an	Jiangsu
China	Affiliated hospital of Xuzhou medical college	Xuzhou	Jiangsu

Sponsors (3)

Lead Sponsor	Collaborator
Kai Lin Xu; Jun Nian Zheng	Huaian first people's hospital, iCarTAB BioMed Inc.

Country where clinical trial is conducted

China, 

References & Publications (2)

Davila ML, Bouhassira DC, Park JH, Curran KJ, Smith EL, Pegram HJ, Brentjens R. Chimeric antigen receptors for the adoptive T cell therapy of hematologic malignancies. Int J Hematol. 2014 Apr;99(4):361-71. doi: 10.1007/s12185-013-1479-5. Epub 2013 Dec 6. — View Citation

van der Stegen SJ, Hamieh M, Sadelain M. The pharmacology of second-generation chimeric antigen receptors. Nat Rev Drug Discov. 2015 Jul;14(7):499-509. doi: 10.1038/nrd4597. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CAR-T cells persistence in peripheral blood	The presence of CAR T cells in patients' peripheral blood will be quantified with real time qPCR	12 months
Secondary	B cell number and immunoglobulins in peripheral blood	The number of B cells and immunoglobulins in peripheral blood will be evaluated by routine methods	12 months