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

Immunotherapy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05354375
• Other study ID #: XYFY2021-KL172-02
• Status: Recruiting
• Phase: Phase 1
• Start date: December 1, 2022
• Est. completion date: November 30, 2026

Study information

• Verified date: November 2021
• Source: The Affiliated Hospital of Xuzhou Medical University
• Contact: Hailong Li, M.D/Ph.D
• Phone: 0086-17798835021
• Email: Justinlee719[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

We designed a clinical study and divided the trial into two phases.

Phase 1 (climbing test): 9 patients were randomly divided into 3 groups (n=3). 9 patients were treated with cyclophosphamide at the dose of 60mg/kg/d 8-7 days before CAR-T cell infusion, and fludalabine at the dose of 25mg/m^2/d 6-2 days before CAR-T cell infusion. On Day 0, CAR T cells were injected into patients in group 1, 2 and 3 at the dose of 1*10^8/ person, 1*10^9/ person and 1*10^10/ person, respectively. The infusion time exceeded 15-30min. On day 0-14, IL-2 (75000IU/kg) was injected subcutaneously once a day. From day 15-28, IL-2 (75000IU/kg) was subcutaneously injected into the patients three times a week. The purpose of this study is to assess subjects' MTD (maximum tolerated dose) against CAR T cells.

Phase 2: After determining the appropriate therapeutic dose for patients with prostate cancer, the remaining 11 patients received the same pre-treatment of chemotherapy. Then, the appropriate therapeutic dose of CAR T cells according to the results of phase 1 was infused on Day 0. On day 0-14,IL-2 (75000IU/kg) was given subcutaneously once a day. On day 15-28, IL-2 (75000IU/kg) was given subcutaneously three times a week.

Subjects will collect peripheral blood every four weeks, detect PSA and other related indicators to evaluate the curative effect, safety and survival rate of CAR-T cell transplantation. After 6 months of close follow-up, the subjects will have a quarterly medical history assessment, physical examination and blood test, bone metastasis assessment by bone ECT, prostate and pelvic cavity assessment by prostate MRI, and general information by PET CT if necessary for two years. After this assessment, the subjects will enter an annual telephone follow-up and questionnaire survey for up to five years to assess the long-term health problems of treatment, such as recurrence of malignant tumors.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: November 30, 2026
• Est. primary completion date: November 30, 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Male patients aged from 18 to 75 years old;

2. The patients' ECOG score = 2;

3. Prostate cancer patients in castration resistance stage (with or without distant metastasis):

1. Previous new endocrine therapy is ineffective;

2. Past treatment with too much citabine or cabatase is ineffective.

4. Have measurable or evaluable lesions;

5. The patients' main tissues and organs function well:

1. Liver function: ALT/AST < 3 times the upper limit of normal value (ULN);

2. renal function: creatinine < 220 µ mol/L;

3. Lung function: indoor oxygen saturation = 95%;

4. Cardiac function: Left ventricular ejection fraction (LVEF)=40%

6. Patients or their legal guardians voluntarily participate and sign the informed consent form.

Exclusion Criteria:

1. Infectious diseases (such as HIV, active hepatitis B or C infection, active tuberculosis, etc.);

2. 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);

3. The vital signs are abnormal and those who cannot cooperate with the inspectors;

4. Those with mental illness or mental illness who can't cooperate with treatment and curative effect evaluation;

5. Highly allergic constitution or severe allergic history, especially those who are allergic to IL-2;

6. Subjects with systemic infection or local severe infection who need anti-infection treatment;

7. Complicated dysfunction of heart, lung, brain, liver, kidney and other important organs;

8. Patients with other tumors;

9. Doctors think that there are other reasons that can't be included in the treatment.

Related Conditions & MeSH terms

• Immunotherapy
• Prostatic Neoplasms

Intervention

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

Locations

Country	Name	City	State
China	Affiliated Hospital of Xuzhou Medical University	Xuzhou	Jiangsu

Sponsors (2)

Lead Sponsor	Collaborator
The Affiliated Hospital of Xuzhou Medical University	Xuzhou Medical University

Country where clinical trial is conducted

China, 

References & Publications (11)

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. Review. — View Citation

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. — View Citation

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 Dete — View Citation

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. — View Citation

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, Rich — View Citation

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

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 J — View Citation

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. Review. — View Citation

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 — View Citation

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. Review. — View Citation

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(1 — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Progression-free Survival (PFS)	Progression-free survival (PFS) time	24 months after CAR-T cells infusion
Secondary	Overall Survival (OS)	Overall survival (OS) time	24 months after CAR-T cells infusion