PD-1 Knockout Engineered T Cells for Castration Resistant Prostate Cancer

NCT02867345 | Withdrawn DMC

• 1 other identifier: 11007965939
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the safety of PD-1 knockout engineered T cells in treating castration resistant prostate cancer (CRPC). Blood samples will also be collected for research purposes.

Conditions

Hormone Refractory Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Response Rate:Response will be evaluated according to RECIST v1.1

  90 days

• 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

• Overall Survival - OS

  The time from randomization to death from any cause, assessed up to 2 years

• Peripheral blood circulating tumor DNA

  6 weeks

• Temporal Interleukin-2 change in the peripheral blood

  Baseline and 1 month and 3 months

Study Arms (2)

Test group

Peripheral blood lymphocytes will be collected and Programmed cell death protein 1(PDCD1) gene will be knocked out by CRISPR Cas9 in the laboratory (PD-1 Knockout T cells). The lymphocytes will be selected and expanded ex vivo and infused back into patients. Cyclophosphamide at 20mg/kg single dose will be administered 3 days i.v. before cell infusion. A total of 2 x 10\^7/kg PD-1 Knockout T cells will be infused in one cycle. Each cycle is divided into three administrations, with 20% infused in the first administration, 30% in the second, and the remaining 50% in the third.Interleukin-2 (IL-2) will be given in the following 5 days, 720000 international unit（IU）/Kg/ day (if tolerant). Patients will receive a total of 2, 3, 4 cycles of treatment.

Biological: PD-1 Knockout T Cells; Drug: Cyclophosphamide; Drug: IL-2

Comparable group

Peripheral blood lymphocytes will be collected and Programmed cell death protein 1(PDCD1) gene will not be knocked out by CRISPR Cas9 in the laboratory (PD-1 Wild-type T cells). The lymphocytes will be selected and expanded ex vivo and infused back into patients. Cyclophosphamide at 20mg/kg single dose will be administered 3 days i.v. before cell infusion. A total of 2 x 10\^7/kg PD-1 wild-type T cells will be infused in one cycle. Each cycle is divided into three administrations, with 20% infused in the first administration, 30% in the second, and the remaining 50% in the third. Interleukin-2 (IL-2) will be given in the following 5 days, 720000 international unit（IU）/Kg/day (if tolerant).

Drug: Cyclophosphamide; Drug: IL-2

Interventions

PD-1 Knockout T Cells BIOLOGICAL

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.

Test group

Cyclophosphamide DRUG

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).

Also known as: cytophosphane

Comparable group; Test group

IL-2 DRUG

Interleukin-2 (IL-2) will be given in the following 5 days after cell infusion, 720000 international unit（IU）/Kg/ day (if tolerant).

Also known as: Interleukin-2 (IL-2)

Comparable group; Test group

Eligibility Criteria

• Age: 45 Years - 85 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologically and clinical verified castration resistant prostate 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
• Willing and able to provide informed consent

You may not qualify if:

• 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

Sponsors & Collaborators

• Peking University: lead

Study Sites (1)

Department of Urology Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

Location

Related Publications (5)

• Taube JM. Unleashing the immune system: PD-1 and PD-Ls in the pre-treatment tumor microenvironment and correlation with response to PD-1/PD-L1 blockade. Oncoimmunology. 2014 Dec 21;3(11):e963413. doi: 10.4161/21624011.2014.963413. eCollection 2014 Nov.

  PMID: 25914862 BACKGROUND

• Yatsuda J, Eto M. [Current status and prospects of immunotherapy for castration-resistant prostate cancer]. Nihon Rinsho. 2014 Dec;72(12):2174-8. Japanese.

  PMID: 25518354 BACKGROUND

• Modena A, Ciccarese C, Iacovelli R, Brunelli M, Montironi R, Fiorentino M, Tortora G, Massari F. Immune Checkpoint Inhibitors and Prostate Cancer: A New Frontier? Oncol Rev. 2016 Apr 15;10(1):293. doi: 10.4081/oncol.2016.293. eCollection 2016 Apr 15.

  PMID: 27471580 RESULT

• Bishop JL, Sio A, Angeles A, Roberts ME, Azad AA, Chi KN, Zoubeidi A. PD-L1 is highly expressed in Enzalutamide resistant prostate cancer. Oncotarget. 2015 Jan 1;6(1):234-42. doi: 10.18632/oncotarget.2703.

  PMID: 25428917 RESULT

• Yi L, Li J. CRISPR-Cas9 therapeutics in cancer: promising strategies and present challenges. Biochim Biophys Acta. 2016 Dec;1866(2):197-207. doi: 10.1016/j.bbcan.2016.09.002. Epub 2016 Sep 15.

  PMID: 27641687 DERIVED

MeSH Terms

Interventions

Cyclophosphamide; Interleukin-2

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 11, 2016
• First Posted: August 15, 2016
• Study Start: November 1, 2016
• Primary Completion: November 1, 2020
• Study Completion: December 1, 2020
• Last Updated: March 6, 2019

Record last verified: 2016-08

Locations

CN (1)