PD-1 Knockout Engineered T Cells for Metastatic Renal Cell Carcinoma.

Metastatic Renal Cell Carcinoma Clinical Trial

Official title:

A Dose-escalation Phase I Trial of PD-1 Knockout Engineered T Cells for the Treatment of Metastatic Renal Cell Carcinoma

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02867332
• Other study ID #: 11007965940
• Status: Withdrawn
• Phase: Phase 1
• Start date: November 2016
• Est. completion date: November 2020

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 renal 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• Status: Withdrawn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: November 2020
• Est. primary completion date: November 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Pathologically verified stage IV Renal 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

• Carcinoma
• Carcinoma, Renal Cell
• Metastatic Renal Cell Carcinoma

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
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Peking University

References & Publications (5)

Bockorny B, Dasanu CA. Intrinsic immune alterations in renal cell carcinoma and emerging immunotherapeutic approaches. Expert Opin Biol Ther. 2013 Jun;13(6):911-25. doi: 10.1517/14712598.2013.778970. Epub 2013 Apr 16. Review. — View Citation

Gandini S, Massi D, Mandalà M. PD-L1 expression in cancer patients receiving anti PD-1/PD-L1 antibodies: A systematic review and meta-analysis. Crit Rev Oncol Hematol. 2016 Apr;100:88-98. doi: 10.1016/j.critrevonc.2016.02.001. Epub 2016 Feb 10. Review. — View Citation

Gunturi A, McDermott DF. Potential of new therapies like anti-PD1 in kidney cancer. Curr Treat Options Oncol. 2014 Mar;15(1):137-46. doi: 10.1007/s11864-013-0268-y. Review. — View Citation

Hofmann L, Forschner A, Loquai C, Goldinger SM, Zimmer L, Ugurel S, Schmidgen MI, Gutzmer R, Utikal JS, Göppner D, Hassel JC, Meier F, Tietze JK, Thomas I, Weishaupt C, Leverkus M, Wahl R, Dietrich U, Garbe C, Kirchberger MC, Eigentler T, Berking C, Gesie — View Citation

Koshkin VS, Rini BI. Emerging therapeutics in refractory renal cell carcinoma. Expert Opin Pharmacother. 2016 Jun;17(9):1225-32. doi: 10.1080/14656566.2016.1182987. Epub 2016 May 23. 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		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