PD-1 Knockout Engineered T Cells for Muscle-invasive Bladder Cancer

Invasive Bladder Cancer Stage IV Clinical Trial

Official title:

A Dose-escalation Phase I Trial of PD-1 Knockout Engineered T Cells for the Treatment of Muscle-invasive Bladder Cancer

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02863913
• Other study ID #: 11007965938
• Status: Withdrawn
• Phase: Phase 1
• Start date: September 2016
• Est. completion date: September 2019

Study information

• Verified date: August 2016
• Source: Peking University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the safety of PD-1 knockout engineered T cells in treating metastatic advanced bladder cancer. Blood samples will also be collected for research purposes.

Description:

This is a dose-escalation study of ex-vivo knocked-out, expanded, and selected PD-1 knockout-T cells from autologous origin. Patients are assigned to 1 of 3 treatment groups to determine the maximal tolerant dose. After the lower number of cycles are considered tolerant, an arm of the next higher number of cycles will be open to next patients. Biomarkers and immunological markers are collected and analyzed as well.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 2019
• Est. primary completion date: September 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Pathologically verified stage IV muscle-invasive bladder cancer with measurable lesions (On CT: longest diameter of tumoral lesion >=10 mm, shorted diameter of lymph node >=15 mm; measurable lesions should not have been irradiated)

• Progressed after all standard treatment

• Performance score: 0-1

• Expected life span: >= 6 months

• Toxicities from prior treatment has resolved. Washout period is 4 weeks for chemotherapy, and 2 weeks for targeted therapy

• Major organs function normally

• Women at pregnant ages should be under contraception

• Willing and able to provide informed consent

Exclusion Criteria:

• Pathology is mixed type

• Emergent treatment of tumor emergency is needed

• Poor vasculature

• Coagulopathy, or ongoing thrombolytics and/or anticoagulation

• Blood-borne infectious disease, e.g. hepatitis B

• History of mandatory custody because of psychosis or other psychological disease inappropriate for treatment deemed by treating physician

• With other immune diseases, or chronic use of immunosuppressants or steroids

• Compliance cannot be expected

• Other conditions requiring exclusion deemed by physician

Related Conditions & MeSH terms

• Invasive Bladder Cancer Stage IV
• Urinary Bladder Neoplasms

Intervention

Biological:
• PD-1 Knockout T Cells
PD-1 Knockout T Cells and PD-1 wild-type T Cells will be made by Cell Biotech Co., Ltd. 2x107/kg T cells will be used for test group and comparable group separately.

Drug:
• Cyclophosphamide
Cyclophosphamide at 20mg/kg single dose will be administered 3 days i.v. before cell infusion. Interleukin-2 (IL-2) will be given in the following 5 days, 720000 international unit(IU)/Kg/day (if tolerant).
• IL-2
Interleukin-2 (IL-2) will be given in the following 5 days after cell infusion, 720000 international unit(IU)/Kg/day (if tolerant).

Locations

Country	Name	City	State
China	Department of Urology Peking University First Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking University

Country where clinical trial is conducted

China, 

References & Publications (6)

Aragon-Ching JB, Trump DL. Systemic therapy in muscle-invasive and metastatic bladder cancer: current trends and future promises. Future Oncol. 2016 Sep;12(17):2049-58. doi: 10.2217/fon-2016-0155. Epub 2016 Jun 16. Review. — View Citation

Bidnur S, Savdie R, Black PC. Inhibiting Immune Checkpoints for the Treatment of Bladder Cancer. Bladder Cancer. 2016 Jan 7;2(1):15-25. Review. — View Citation

Donin NM, Lenis AT, Holden S, Drakaki A, Pantuck A, Belldegrun A, Chamie K. Immunotherapy for the Treatment of Urothelial Carcinoma. J Urol. 2017 Jan;197(1):14-22. doi: 10.1016/j.juro.2016.02.3005. Epub 2016 Jul 25. Review. — View Citation

Festino L, Botti G, Lorigan P, Masucci GV, Hipp JD, Horak CE, Melero I, Ascierto PA. Cancer Treatment with Anti-PD-1/PD-L1 Agents: Is PD-L1 Expression a Biomarker for Patient Selection? Drugs. 2016 Jun;76(9):925-45. doi: 10.1007/s40265-016-0588-x. Review. — View Citation

Kim J. Immune checkpoint blockade therapy for bladder cancer treatment. Investig Clin Urol. 2016 Jun;57 Suppl 1:S98-S105. doi: 10.4111/icu.2016.57.S1.S98. Epub 2016 May 26. Review. — View Citation

Zibelman M, Plimack ER. Systemic therapy for bladder cancer finally comes into a new age. Future Oncol. 2016 Oct;12(19):2227-42. doi: 10.2217/fon-2016-0135. Epub 2016 Jul 12. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with Adverse Events and/or Dose Limiting Toxicities as a Measure of Safety and tolerability of dose of PD-1 Knockout T cells using Common Terminology Criteria for Adverse Events (CTCAE v4.0) in patients		Dose Escalation - Approximately 6 months
Secondary	Response Rate:Response will be evaluated according to RECIST v1.1		90 days
Secondary	Progression free survival - PFS		From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to average 10 months
Secondary	Overall Survival - OS		The time from randomization to death from any cause, assessed up to 2 years
Secondary	Peripheral blood circulating tumor DNA	Peripheral circuiting tumor DNA is collected at baseline and 6 weeks after last treatment	6 weeks
Secondary	Temporal Interleukin-2 change in the peripheral blood		Baseline and 1 month and 3 months
Secondary	Temporal Interferon-? change in the peripheral blood		Baseline and 1 month and 3 months
Secondary	Temporal Interleukin-6 change in the peripheral blood		Baseline and 1 month and 3 months