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Anti-MUC1 CAR T Cells and PD-1 Knockout Engineered T Cells for NSCLC

Primary Purpose

Lung Neoplasm Malignant, Non-small Cell Lung Cancer

Status

Unknown status

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

CAR-T Cells

CAR-T combining PD-1 Knockout

PD-1 knockout

PD-1 mAb

Sham control

About this trial

This is an interventional treatment trial for Lung Neoplasm Malignant focused on measuring CAR-T cell therapy, MUC+, PD-1 Knockout, Non-small cell lung cancer

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

MUC1 is expressed in malignancy tissues by immuno-histochemical (IHC).
Eastern cooperative oncology group (ECOG) performance status of 0-1 or karnofsky performance status (KPS) score is higher than 60.
Patients have a life expectancy > 12 weeks.
Adequate venous access for apheresis or venous sampling, and no other contraindications for leukapheresis.
Negative pregnancy test for females of child-bearing potentials.
Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements: White blood cell count (WBC) ≥ 2500c/ml, Platelets ≥ 50×10^9/L, Hb ≥ 9.0g/dL, lymphocyte (LY) ≥ 0.7×10^9/L, LY% ≥ 15%, Alb ≥ 2.8g/dL, serum lipase and amylase < 1.5×upper limit of normal, serum creatinine ≤ 2.5mg/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5×upper limit of normal, serum total bilirubin ≤ 2.0mg/dL. These tests must be conducted within 7 days prior to registration.
Signed informed consent form.

Exclusion Criteria:

Number of T cells is less than 10% or the amplification of the T cells via artificial antigen presenting cell (aAPC) stimulation is less than 5 times.
Patients with symptomatic central nervous system (CNS) involvement.
Pregnant or nursing women.
Known HIV infection.
Serious illness or medical condition which would not permit the patient to be managed according to the protocol, including active uncontrolled infection, major cardiovascular, coagulation disorders, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive/restrictive pulmonary disease, or psychiatric or emotional disorders.
History of severe immediate hypersensitivity to any of the agents including cyclophosphamide, fludarabine, or aldesleukin.
Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.
Previously treatment with any gene therapy products.
The existence of unstable or active ulcers or gastrointestinal bleeding. Patients with portal vein vascular invasion or extrahepatic, are excluded from this study.
Patients with a history of organ transplantation or are waiting for organ transplantation.

Sites / Locations

First Affiliated Hospital of Guangdong Pharmaceutical UniversityRecruiting
Professor Size ChenRecruiting
Professor Size ChenRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Active Comparator

Placebo Comparator

Arm Label

CAR-T

CAR-T combining PD-1 knockout

PD-1 knockout

PD-1 mAb

Sham Control

Arm Description

Anti-MUC1 CAR-T cells will be prepared ex vivo and infused back to the patients.

Anti-MUC1 CAR-T cells and PD-1 knockout Engineered T cells will be prepared ex vivo and infused back to the patients.

PD-1 knockout Engineered T cells will be prepared ex vivo and infused back to the patients.

Patients will be treated with a FDA approved monoclonal antibody for an identical course of treatment. This group will serve as PD-1 antibody treated group.

Patient's T cells will be separate without genetic or engineered modification ex vivo and infused back to the patients.

Outcomes

Primary Outcome Measures

Number of participants with adverse events and dose limiting toxicities as assessed by CTCAE v4.0

Safety and tolerability of dose of CART-cells and PD-1 Knockout T cells will be assessed using CTCAE v4.0.

Secondary Outcome Measures

Response Rate

Will be assessed according to the revised RECIST guideline v1.1

Overall Survival - OS

Measure the time from enrollment to death

Progression free survival - PFS

Time from enrollment to date of first documented progression or date of death.

Median CAR-T cell persistence

Will be measured by quantitative RT-PCR

Full Information

NCT ID

NCT03525782

First Posted

April 26, 2018

Last Updated

May 3, 2018

Sponsor

The First Affiliated Hospital of Guangdong Pharmaceutical University

Collaborators

Guangzhou Anjie Biomedical Technology Co., Ltd., University of Technology, Sydney

1. Study Identification

Unique Protocol Identification Number

NCT03525782

Brief Title

Anti-MUC1 CAR T Cells and PD-1 Knockout Engineered T Cells for NSCLC

Official Title

A Clinical Study of Anti-MUC1 CAR T Cells and PD-1 Knockout Engineered T Cells for Patients With Advanced Non-small Cell Lung Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

May 2018

Overall Recruitment Status

Unknown status

Study Start Date

February 1, 2018 (Actual)

Primary Completion Date

January 31, 2021 (Anticipated)

Study Completion Date

January 31, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

The First Affiliated Hospital of Guangdong Pharmaceutical University

Collaborators

Guangzhou Anjie Biomedical Technology Co., Ltd., University of Technology, Sydney

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The study is to assess the safety and efficacy of the anti-MUC1 CAR T cells and /or PD-1 knockout engineered T cells for patients with advanced non-small cell lung cancer.

Detailed Description

This is a combined phase 1 and 2 clinical study. The study is to assess the safety and efficacy of the anti-MUC1 CAR T cells and /or PD-1 knockout engineered T cells for patients with advanced non-small cell lung cancer. The treatment outcomes will be compared.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lung Neoplasm Malignant, Non-small Cell Lung Cancer

Keywords

CAR-T cell therapy, MUC+, PD-1 Knockout, Non-small cell lung cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

Participant

Allocation

Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

CAR-T

Arm Type

Experimental

Arm Description

Anti-MUC1 CAR-T cells will be prepared ex vivo and infused back to the patients.

Arm Title

CAR-T combining PD-1 knockout

Arm Type

Experimental

Arm Description

Anti-MUC1 CAR-T cells and PD-1 knockout Engineered T cells will be prepared ex vivo and infused back to the patients.

Arm Title

PD-1 knockout

Arm Type

Experimental

Arm Description

PD-1 knockout Engineered T cells will be prepared ex vivo and infused back to the patients.

Arm Title

PD-1 mAb

Arm Type

Active Comparator

Arm Description

Patients will be treated with a FDA approved monoclonal antibody for an identical course of treatment. This group will serve as PD-1 antibody treated group.

Arm Title

Sham Control

Arm Type

Placebo Comparator

Arm Description

Patient's T cells will be separate without genetic or engineered modification ex vivo and infused back to the patients.

Intervention Type

Biological

Intervention Name(s)

CAR-T Cells

Intervention Description

Using the T cells from the patients to produce anti-MUC1 CAR-T Cells and then the cells will be infused back to the patients.

Intervention Type

Combination Product

Intervention Name(s)

CAR-T combining PD-1 Knockout

Intervention Description

Using the T cells from the patients to prepare anti-MUC1 CAR-T Cells and PD-1 knockout T cells, then the cells will be infused back to the patients

Intervention Type

Biological

Intervention Name(s)

PD-1 knockout

Intervention Description

Using the T cells from the patients to prepare PD-1 knockout T cells, then the cells will be infused back to the patients

Intervention Type

Drug

Intervention Name(s)

PD-1 mAb

Other Intervention Name(s)

Keytruda

Intervention Description

Patients will be treated with an identical course with a FDA approved monoclonal antibody against PD-1

Intervention Type

Other

Intervention Name(s)

Sham control

Intervention Description

Patient's T cell will treated ex vivo with modification and then infused back in a similar time course.

Primary Outcome Measure Information:

Title

Number of participants with adverse events and dose limiting toxicities as assessed by CTCAE v4.0

Description

Safety and tolerability of dose of CART-cells and PD-1 Knockout T cells will be assessed using CTCAE v4.0.

Time Frame

approximately 6 months

Secondary Outcome Measure Information:

Title

Response Rate

Description

Will be assessed according to the revised RECIST guideline v1.1

Time Frame

6 months

Title

Overall Survival - OS

Description

Measure the time from enrollment to death

Time Frame

Up to 24 months

Title

Progression free survival - PFS

Description

Time from enrollment to date of first documented progression or date of death.

Time Frame

Up to 12 months

Title

Median CAR-T cell persistence

Description

Will be measured by quantitative RT-PCR

Time Frame

4 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: MUC1 is expressed in malignancy tissues by immuno-histochemical (IHC). Eastern cooperative oncology group (ECOG) performance status of 0-1 or karnofsky performance status (KPS) score is higher than 60. Patients have a life expectancy > 12 weeks. Adequate venous access for apheresis or venous sampling, and no other contraindications for leukapheresis. Negative pregnancy test for females of child-bearing potentials. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements: White blood cell count (WBC) ≥ 2500c/ml, Platelets ≥ 50×10^9/L, Hb ≥ 9.0g/dL, lymphocyte (LY) ≥ 0.7×10^9/L, LY% ≥ 15%, Alb ≥ 2.8g/dL, serum lipase and amylase < 1.5×upper limit of normal, serum creatinine ≤ 2.5mg/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5×upper limit of normal, serum total bilirubin ≤ 2.0mg/dL. These tests must be conducted within 7 days prior to registration. Signed informed consent form. Exclusion Criteria: Number of T cells is less than 10% or the amplification of the T cells via artificial antigen presenting cell (aAPC) stimulation is less than 5 times. Patients with symptomatic central nervous system (CNS) involvement. Pregnant or nursing women. Known HIV infection. Serious illness or medical condition which would not permit the patient to be managed according to the protocol, including active uncontrolled infection, major cardiovascular, coagulation disorders, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive/restrictive pulmonary disease, or psychiatric or emotional disorders. History of severe immediate hypersensitivity to any of the agents including cyclophosphamide, fludarabine, or aldesleukin. Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary. Previously treatment with any gene therapy products. The existence of unstable or active ulcers or gastrointestinal bleeding. Patients with portal vein vascular invasion or extrahepatic, are excluded from this study. Patients with a history of organ transplantation or are waiting for organ transplantation.

Facility Information:

Facility Name

First Affiliated Hospital of Guangdong Pharmaceutical University

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510080

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Guobiao Huang

Phone

86-20-39352064

153706227@qq.com

Facility Name

Professor Size Chen

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510080

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Size Chen, MD,PhD

Phone

+8613720956393

13720956393@139.com

First Name & Middle Initial & Last Name & Degree

Zhizhou Huang, MSc

Phone

+8613268258980

hzhizhou@sina.com

First Name & Middle Initial & Last Name & Degree

Yiguang Lin, MD, PhD

First Name & Middle Initial & Last Name & Degree

Size Chen, MD, PhD

First Name & Middle Initial & Last Name & Degree

Micheal Yin, PhD

Facility Name

Professor Size Chen

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510080

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Size Chen, MD,PhD

Phone

+8613720956393

13720956393@139.com

First Name & Middle Initial & Last Name & Degree

Yiguang Lin, MD, PhD

First Name & Middle Initial & Last Name & Degree

Micheal Yin, PhD

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Anti-MUC1 CAR T Cells and PD-1 Knockout Engineered T Cells for NSCLC

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