Humanized CAR-T Therapy for Treatment of B Cell Malignancy

Sponsor

Kai Lin Xu; Jun Nian Zheng (Other)

Overall Status

Unknown status

CT.gov ID

NCT02782351

Collaborator

iCarTAB BioMed Inc. (Other), Huaian first people's hospital (Other)

Enrollment

Locations

Arm

Duration (Months)

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia, Lymphocytic, Chronic, B-Cell	Biological: CAR-T	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

May 1, 2016

Anticipated Primary Completion Date :

Jun 1, 2018

Anticipated Study Completion Date :

Dec 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Biological: CAR-T Patients will be infused with autologous CAR-T infusion in a dose escalating manner.

Arm

Intervention/Treatment

Experimental: 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.

Biological: CAR-T

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

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Huaian First People's Hospital	Huai'an	Jiangsu	China	223300
2	Affiliated hospital of Xuzhou medical college	Xuzhou	Jiangsu	China	221000

Sponsors and Collaborators

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

Investigators

Principal Investigator: KaiLin Xu, MD. Ph.D., Xuzhou Medical University

Study Documents (Full-Text)

None provided.

More Information

Publications

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.

Responsible Party:

Kai Lin Xu; Jun Nian Zheng, President, Xuzhou Medical University

ClinicalTrials.gov Identifier:

NCT02782351

Other Study ID Numbers:

XYFY2016-KL002-01

First Posted:

May 25, 2016

Last Update Posted:

Aug 4, 2017

Last Verified:

Aug 1, 2017

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Additional relevant MeSH terms:

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Study Results

No Results Posted as of Aug 4, 2017