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Humanized CAR-T Therapy for Treatment of B Cell Malignancy

Primary Purpose

Leukemia, Lymphocytic, Chronic, B-Cell

Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
CAR-T
Sponsored by
Kai Lin Xu; Jun Nian Zheng
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia, Lymphocytic, Chronic, B-Cell

Eligibility Criteria

3 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Huaian First People's HospitalRecruiting
  • Affiliated hospital of Xuzhou medical collegeRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CAR-T

Arm Description

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

Outcomes

Primary Outcome Measures

CAR-T cells persistence in peripheral blood
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
The number of B cells and immunoglobulins in peripheral blood will be evaluated by routine methods

Full Information

First Posted
May 17, 2016
Last Updated
August 3, 2017
Sponsor
Kai Lin Xu; Jun Nian Zheng
Collaborators
iCarTAB BioMed Inc., Huaian first people's hospital
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1. Study Identification

Unique Protocol Identification Number
NCT02782351
Brief Title
Humanized CAR-T Therapy for Treatment of B Cell Malignancy
Official Title
Humanized CAR-T Therapy for Treatment of Recurrent or Refractory B Cell Malignancy by Targeting CD19
Study Type
Interventional

2. Study Status

Record Verification Date
August 2017
Overall Recruitment Status
Unknown status
Study Start Date
May 2016 (undefined)
Primary Completion Date
June 2018 (Anticipated)
Study Completion Date
December 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Kai Lin Xu; Jun Nian Zheng
Collaborators
iCarTAB BioMed Inc., Huaian first people's hospital

4. Oversight

Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphocytic, Chronic, B-Cell

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CAR-T
Arm Type
Experimental
Arm Description
In interventional studies, patients enrolled will receive autologous 2nd generation CAR-T cells, which contain a humanized single chain antibody sequence against CD19.
Intervention Type
Biological
Intervention Name(s)
CAR-T
Intervention Description
Patients will be infused with autologous CAR-T infusion in a dose escalating manner.
Primary Outcome Measure Information:
Title
CAR-T cells persistence in peripheral blood
Description
The presence of CAR T cells in patients' peripheral blood will be quantified with real time qPCR
Time Frame
12 months
Secondary Outcome Measure Information:
Title
B cell number and immunoglobulins in peripheral blood
Description
The number of B cells and immunoglobulins in peripheral blood will be evaluated by routine methods
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jiang Cao, M.D., Ph.D.
Phone
8651685802291
Email
zimu05067@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
JunNian Zheng, M.D., Ph.D.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
KaiLin Xu, MD. Ph.D.
Organizational Affiliation
Xuzhou Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Huaian First People's Hospital
City
Huai'an
State/Province
Jiangsu
ZIP/Postal Code
223300
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chunling Wang, M.D., Ph.D.
Facility Name
Affiliated hospital of Xuzhou medical college
City
Xuzhou
State/Province
Jiangsu
ZIP/Postal Code
221000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jiang Cao, M.D., Ph.D.

12. IPD Sharing Statement

Plan to Share IPD
Yes
Citations:
PubMed Identifier
26129802
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.
Results Reference
background
PubMed Identifier
24311149
Citation
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.
Results Reference
result
PubMed Identifier
35338773
Citation
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.
Results Reference
derived
PubMed Identifier
34777367
Citation
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.
Results Reference
derived

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Humanized CAR-T Therapy for Treatment of B Cell Malignancy

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