Clinical Study of CAIX-targeted CAR-T Cells in the Treatment of Advanced Renal Cell Carcinoma

NCT04969354 | Recruiting Phase 1 DMC

• 1 other identifier: XYFY2021-KL092-02
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is an experimental study to evaluate the safety and efficacy of CAR T cells targeting CAIX in the treatment of advanced renal cancer.

Conditions

Immunotherapy

Keywords

Carbonic anhydrase; advanced renal cell carcinoma; CAR-T; Chimeric antigen receptor; T cell; CAIX

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 CAIX 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 received CAR-T cell immunotherapy for the new specific chimeric antigen receptor of CAIX 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 CAIX antigen.

CAR-T cell immunotherapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged from 18 to 70 years old;
• The patient's ECOG score is ≤ 2;
• Patients with advanced or metastatic renal cell carcinoma:
• (1) have received first-line and second-line targeted therapy in the past; (2) Previous immunization with PD-1/L1 and ≤2 regimens; (3) Unable to tolerate targeted therapy or immunotherapy. 4.There are measurable or evaluable lesions; 5.The main tissues and organs of patients function well:
• liver function: ALT/AST\< 3 times the upper limit of normal value (ULN);
• Renal function: creatinine \< 220 μmol/L;
• Lung function: indoor oxygen saturation ≥ 95%;
• Cardiac function: Left ventricular ejection fraction (LVEF)≥40% 6.Patients or their legal guardians voluntarily participate and sign informed consent.

You may not qualify if:

• Infectious diseases (such as HIV, active hepatitis B or C infection, active tuberculosis, etc.);
• Feasibility assessment and screening showed that the transfection of targeted lymphocytes was less than 10% or the amplification was insufficient (\< 5 times) under the co-stimulation of CD3/CD28.
• The vital signs are abnormal, and those who cannot cooperate with the examination;
• Those who have mental or psychological diseases can not cooperate with treatment and efficacy evaluation;
• Highly allergic constitution or severe allergic history, especially those who are allergic to IL-2;
• Subjects with systemic infection or severe local infection who need anti-infection treatment;
• Complicated with dysfunction of heart, lung, brain, liver, kidney and other important organs;
• Patients with other tumors;
• Doctors believe that there are other reasons that can not 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 (12)

• Linehan WM, Ricketts CJ. Kidney cancer in 2016: RCC - advances in targeted therapeutics and genomics. Nat Rev Urol. 2017 Feb;14(2):76-78. doi: 10.1038/nrurol.2016.260. Epub 2016 Dec 29. No abstract available.

  PMID: 28031562 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

• Weinkove R, George P, Dasyam N, McLellan AD. Selecting costimulatory domains for chimeric antigen receptors: functional and clinical considerations. Clin Transl Immunology. 2019 May 11;8(5):e1049. doi: 10.1002/cti2.1049. eCollection 2019.

  PMID: 31110702 RESULT

• Brentjens RJ, Davila ML, Riviere I, Park J, Wang X, Cowell LG, Bartido S, Stefanski J, Taylor C, Olszewska M, Borquez-Ojeda O, Qu J, Wasielewska T, He Q, Bernal Y, Rijo IV, Hedvat C, Kobos R, Curran K, Steinherz P, Jurcic J, Rosenblat T, Maslak P, Frattini M, Sadelain M. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med. 2013 Mar 20;5(177):177ra38. doi: 10.1126/scitranslmed.3005930.

  PMID: 23515080 RESULT

• Song C, Sadashivaiah K, Furusawa A, Davila E, Tamada K, Banerjee A. Eomesodermin is required for antitumor immunity mediated by 4-1BB-agonist immunotherapy. Oncoimmunology. 2014 Jan 1;3(1):e27680. doi: 10.4161/onci.27680. Epub 2014 Feb 27.

  PMID: 24790793 RESULT

• Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, Chew A, Gonzalez VE, Zheng Z, Lacey SF, Mahnke YD, Melenhorst JJ, Rheingold SR, Shen A, Teachey DT, Levine BL, June CH, Porter DL, Grupp SA. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014 Oct 16;371(16):1507-17. doi: 10.1056/NEJMoa1407222.

  PMID: 25317870 RESULT

• Kawalekar OU, O' Connor RS, Fraietta JA, Guo L, McGettigan SE, Posey AD Jr, Patel PR, Guedan S, Scholler J, Keith B, Snyder NW, Blair IA, Milone MC, June CH. Distinct Signaling of Coreceptors Regulates Specific Metabolism Pathways and Impacts Memory Development in CAR T Cells. Immunity. 2016 Mar 15;44(3):712. doi: 10.1016/j.immuni.2016.02.023. Epub 2016 Mar 15. No abstract available.

  PMID: 28843072 RESULT

• Long AH, Haso WM, Shern JF, Wanhainen KM, Murgai M, Ingaramo M, Smith JP, Walker AJ, Kohler ME, Venkateshwara VR, Kaplan RN, Patterson GH, Fry TJ, Orentas RJ, Mackall CL. 4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors. Nat Med. 2015 Jun;21(6):581-90. doi: 10.1038/nm.3838. Epub 2015 May 4.

  PMID: 25939063 RESULT

• Lamers CH, Sleijfer S, van Steenbergen S, van Elzakker P, van Krimpen B, Groot C, Vulto A, den Bakker M, Oosterwijk E, Debets R, Gratama JW. Treatment of metastatic renal cell carcinoma with CAIX CAR-engineered T cells: clinical evaluation and management of on-target toxicity. Mol Ther. 2013 Apr;21(4):904-12. doi: 10.1038/mt.2013.17. Epub 2013 Feb 19.

  PMID: 23423337 RESULT

• Lamers CH, Willemsen R, van Elzakker P, van Steenbergen-Langeveld S, Broertjes M, Oosterwijk-Wakka J, Oosterwijk E, Sleijfer S, Debets R, Gratama JW. Immune responses to transgene and retroviral vector in patients treated with ex vivo-engineered T cells. Blood. 2011 Jan 6;117(1):72-82. doi: 10.1182/blood-2010-07-294520. Epub 2010 Oct 1.

  PMID: 20889925 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: July 4, 2021
• First Posted: July 20, 2021
• Study Start: October 1, 2021
• Primary Completion: September 30, 2025
• Study Completion (Estimated): September 30, 2026
• Last Updated: July 20, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)