Clinical trial NCT02782351: 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
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Leukemia, Lymphocytic, Chronic, B-Cell
Lead sponsor: Xuzhou Medical University
Sponsor class: OTHER
Collaborators: name: iCarTAB BioMed Inc.
name: Huaian first people's hospital
First posted: 2016-05-25
Enrollment: 50
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: CAR-T cells persistence in peripheral blood
timeFrame: 12 months
Secondary outcomes:
measure: B cell number and immunoglobulins in peripheral blood
timeFrame: 12 months
Other outcomes:
Locations:
city: Huai'an
country: China
facility: Huaian First People's Hospital
state: Jiangsu
city: Xuzhou
country: China
facility: Affiliated hospital of Xuzhou medical college
state: Jiangsu
Study officials:
affiliation: Xuzhou Medical University
name: KaiLin Xu, MD. Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.