Clinical Study of PSMA-targeted CAR-T Cells in the Treatment of Castration-resistant Prostate Cancer

NCT05354375 | Recruiting Phase 1 DMC

• 1 other identifier: XYFY2021-KL172-02
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is an experimental study to evaluate the safety and effectiveness of PSMA-targeted CAR-T cells in the treatment of castration-resistant prostate cancer.

Conditions

Immunotherapy

Keywords

Prostate specific membrane antigen; Castration-resistant Prostate Cancer; CAR-T; Chimeric antigen receptor; T cell

Outcome Measures

Primary Outcomes (2)

• Safety Evaluation:Incidence and Severity of Adverse Events

  To evaluate the incidence and severity of possible adverse events within one month after targeted PSMA CAR-T infusion, including cytokine release syndrome and on-target toxicity.

  First 1 month after CAR-T cells infusion

• Effectiveness Evaluation

  In order to observe the efficacy of CAR-T cells after infusion, total remission rate (ORR), complete remission (CR), partial remission (PR), disease stability (SD) or progression (PD) will be used for evaluation.

  3 months after CAR-T cells infusion

Secondary Outcomes (2)

• Progression-free Survival (PFS)

  24 months after CAR-T cells infusion

• Overall Survival (OS)

  24 months after CAR-T cells infusion

Study Arms (1)

CAR-T cell immunotherapy

EXPERIMENTAL

The registered patients will receive CAR-T cell immunotherapy for the new specific chimeric antigen receptor of PSMA antigen by infusion.

Biological: CAR-T cell immunotherapy

Interventions

CAR-T cell immunotherapy BIOLOGICAL

This CAR-T cell immunotherapy with a novel specific Chimeric antigen receptor aiming at PSMA.

CAR-T cell immunotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male patients aged from 18 to 75 years old;
• The patients' ECOG score ≤ 2;
• Prostate cancer patients in castration resistance stage (with or without distant metastasis):
• Previous new endocrine therapy is ineffective;
• Past treatment with too much citabine or cabatase is ineffective.
• Have measurable or evaluable lesions;
• The patients' main tissues and organs function well:
• Liver function: ALT/AST \< 3 times the upper limit of normal value (ULN);
• renal function: creatinine \< 220 μ mol/L;
• Lung function: indoor oxygen saturation ≥ 95%;
• Cardiac function: Left ventricular ejection fraction (LVEF)≥40%
• Patients or their legal guardians voluntarily participate and sign the informed consent form.

You may not qualify if:

• Infectious diseases (such as HIV, active hepatitis B or C infection, active tuberculosis, etc.);
• Feasibility evaluation screening proves that the transfection of targeted lymphocytes is less than 10% or the amplification under the co-stimulation of CD3/CD28 is insufficient (\< 5 times);
• The vital signs are abnormal and those who cannot cooperate with the inspectors;
• Those with mental illness or mental illness who can't cooperate with treatment and curative effect evaluation;
• Highly allergic constitution or severe allergic history, especially those who are allergic to IL-2;
• Subjects with systemic infection or local severe infection who need anti-infection treatment;
• Complicated dysfunction of heart, lung, brain, liver, kidney and other important organs;
• Patients with other tumors;
• Doctors think that there are other reasons that can't be included in the treatment.

Sponsors & Collaborators

• The Affiliated Hospital of Xuzhou Medical University: lead
• Xuzhou Medical University: collaborator

Study Sites (1)

Affiliated Hospital of Xuzhou Medical University

Xuzhou, Jiangsu, 221000, China

RECRUITING

Related Publications (11)

• Mohler JL, Antonarakis ES, Armstrong AJ, D'Amico AV, Davis BJ, Dorff T, Eastham JA, Enke CA, Farrington TA, Higano CS, Horwitz EM, Hurwitz M, Ippolito JE, Kane CJ, Kuettel MR, Lang JM, McKenney J, Netto G, Penson DF, Plimack ER, Pow-Sang JM, Pugh TJ, Richey S, Roach M, Rosenfeld S, Schaeffer E, Shabsigh A, Small EJ, Spratt DE, Srinivas S, Tward J, Shead DA, Freedman-Cass DA. Prostate Cancer, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2019 May 1;17(5):479-505. doi: 10.6004/jnccn.2019.0023.

  PMID: 31085757 RESULT

• Gansler T, Ganz PA, Grant M, Greene FL, Johnstone P, Mahoney M, Newman LA, Oh WK, Thomas CR Jr, Thun MJ, Vickers AJ, Wender RC, Brawley OW. Sixty years of CA: a cancer journal for clinicians. CA Cancer J Clin. 2010 Nov-Dec;60(6):345-50. doi: 10.3322/caac.20088.

  PMID: 21075954 RESULT

• Slovin SF. Immunotherapy for castration-resistant prostate cancer: has its time arrived? Expert Opin Biol Ther. 2020 May;20(5):481-487. doi: 10.1080/14712598.2020.1735345. Epub 2020 Mar 5.

  PMID: 32097050 RESULT

• Esmaeilzadeh A, Tahmasebi S, Athari SS. Chimeric antigen receptor -T cell therapy: Applications and challenges in treatment of allergy and asthma. Biomed Pharmacother. 2020 Mar;123:109685. doi: 10.1016/j.biopha.2019.109685. Epub 2019 Dec 17.

  PMID: 31862474 RESULT

• Zuccolotto G, Fracasso G, Merlo A, Montagner IM, Rondina M, Bobisse S, Figini M, Cingarlini S, Colombatti M, Zanovello P, Rosato A. PSMA-specific CAR-engineered T cells eradicate disseminated prostate cancer in preclinical models. PLoS One. 2014 Oct 3;9(10):e109427. doi: 10.1371/journal.pone.0109427. eCollection 2014.

  PMID: 25279468 RESULT

• Minn I, Huss DJ, Ahn HH, Chinn TM, Park A, Jones J, Brummet M, Rowe SP, Sysa-Shah P, Du Y, Levitsky HI, Pomper MG. Imaging CAR T cell therapy with PSMA-targeted positron emission tomography. Sci Adv. 2019 Jul 3;5(7):eaaw5096. doi: 10.1126/sciadv.aaw5096. eCollection 2019 Jul.

  PMID: 31281894 RESULT

• Santoro SP, Kim S, Motz GT, Alatzoglou D, Li C, Irving M, Powell DJ Jr, Coukos G. T cells bearing a chimeric antigen receptor against prostate-specific membrane antigen mediate vascular disruption and result in tumor regression. Cancer Immunol Res. 2015 Jan;3(1):68-84. doi: 10.1158/2326-6066.CIR-14-0192. Epub 2014 Oct 30.

  PMID: 25358763 RESULT

• Zhang Q, Li H, Yang J, Li L, Zhang B, Li J, Zheng J. Strategies to improve the clinical performance of chimeric antigen receptor-modified T cells for cancer. Curr Gene Ther. 2013 Feb;13(1):65-70. doi: 10.2174/156652313804806570.

  PMID: 23256743 RESULT

• Sadelain M, Riviere I, Riddell S. Therapeutic T cell engineering. Nature. 2017 May 24;545(7655):423-431. doi: 10.1038/nature22395.

  PMID: 28541315 RESULT

• Xu J, Tian K, Zhang H, Li L, Liu H, Liu J, Zhang Q, Zheng J. Chimeric antigen receptor-T cell therapy for solid tumors require new clinical regimens. Expert Rev Anticancer Ther. 2017 Dec;17(12):1099-1106. doi: 10.1080/14737140.2017.1395285. Epub 2017 Oct 26.

  PMID: 29048935 RESULT

• Junghans RP, Ma Q, Rathore R, Gomes EM, Bais AJ, Lo AS, Abedi M, Davies RA, Cabral HJ, Al-Homsi AS, Cohen SI. Phase I Trial of Anti-PSMA Designer CAR-T Cells in Prostate Cancer: Possible Role for Interacting Interleukin 2-T Cell Pharmacodynamics as a Determinant of Clinical Response. Prostate. 2016 Oct;76(14):1257-70. doi: 10.1002/pros.23214. Epub 2016 Jun 21.

  PMID: 27324746 RESULT

MeSH Terms

Interventions

Immunotherapy, Adoptive

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Study Officials

• Junnian Zheng, M.D/Ph.D

  The Affiliated Hospital of Xuzhou Medical University

  STUDY DIRECTOR

• Hailong Li, M.D/Ph.D

  The Affiliated Hospital of Xuzhou Medical University

  PRINCIPAL INVESTIGATOR

• Qing Zhang, Ph.D

  Xuzhou Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hailong Li, M.D/Ph.D

CONTACT

0086-17798835021; Justinlee719@163.com

Qing Zhang, Ph.D

CONTACT

0086-516-83262238; qingzhang@xzhmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2022
• First Posted: April 29, 2022
• Study Start: December 1, 2022
• Primary Completion: November 30, 2025
• Study Completion (Estimated): November 30, 2026
• Last Updated: April 29, 2022

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)