Humanized CAR-T Therapy for Treatment of B Cell Malignancy

NCT ID: NCT02782351

Last Updated: 2017-08-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1/PHASE2

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-05-31

Study Completion Date

2018-12-31

Brief Summary

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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

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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.

Conditions

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Leukemia, Lymphocytic, Chronic, B-Cell

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

CAR-T

Intervention Type BIOLOGICAL

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

Interventions

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CAR-T

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

Intervention Type BIOLOGICAL

Eligibility Criteria

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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
Minimum Eligible Age

3 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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iCarTAB BioMed Inc.

UNKNOWN

Sponsor Role collaborator

Huaian first people's hospital

UNKNOWN

Sponsor Role collaborator

Kai Lin Xu; Jun Nian Zheng

OTHER

Sponsor Role lead

Responsible Party

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Kai Lin Xu; Jun Nian Zheng

President

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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KaiLin Xu, MD. Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Xuzhou Medical University

Locations

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Huaian First People's Hospital

Huai'an, Jiangsu, China

Site Status RECRUITING

Affiliated hospital of Xuzhou medical college

Xuzhou, Jiangsu, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Jiang Cao, M.D., Ph.D.

Role: CONTACT

8651685802291

JunNian Zheng, M.D., Ph.D.

Role: CONTACT

Facility Contacts

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Chunling Wang, M.D., Ph.D.

Role: primary

Jiang Cao, M.D., Ph.D.

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 26129802 (View on PubMed)

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.

Reference Type RESULT
PMID: 24311149 (View on PubMed)

Qi Y, Zhao M, Hu Y, Wang Y, Li P, Cao J, Shi M, Tan J, Zhang M, Xiao X, Xia J, Ma S, Qiao J, Yan Z, Li H, Pan B, Sang W, Li D, Li Z, Zhou J, Huang H, Liang A, Zheng J, Xu K. Efficacy and safety of CD19-specific CAR T cell-based therapy in B-cell acute lymphoblastic leukemia patients with CNSL. Blood. 2022 Jun 9;139(23):3376-3386. doi: 10.1182/blood.2021013733.

Reference Type DERIVED
PMID: 35338773 (View on PubMed)

Chen W, Ma Y, Shen Z, Chen H, Ma R, Yan D, Shi M, Wang X, Song X, Sun C, Cao J, Cheng H, Zhu F, Sun H, Li D, Li Z, Zheng J, Xu K, Sang W. Humanized Anti-CD19 CAR-T Cell Therapy and Sequential Allogeneic Hematopoietic Stem Cell Transplantation Achieved Long-Term Survival in Refractory and Relapsed B Lymphocytic Leukemia: A Retrospective Study of CAR-T Cell Therapy. Front Immunol. 2021 Oct 29;12:755549. doi: 10.3389/fimmu.2021.755549. eCollection 2021.

Reference Type DERIVED
PMID: 34777367 (View on PubMed)

Other Identifiers

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XYFY2016-KL002-01

Identifier Type: -

Identifier Source: org_study_id

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