Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
ClinicalTrials.gov
ClinicalTrials.gov Menu

CTLA-4 and PD-1 Antibodies Expressing MUC1-CAR-T Cells for MUC1 Positive Advanced Solid Tumor

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03179007
Recruitment Status : Unknown
Verified June 2017 by Shanghai Cell Therapy Research Institute.
Recruitment status was:  Recruiting
First Posted : June 7, 2017
Last Update Posted : June 7, 2017
Sponsor:
Information provided by (Responsible Party):
Shanghai Cell Therapy Research Institute

Brief Summary:
This is a single-arm, open-label, one center clinical study, to determine the safety and efficacy of infusion of autologous T cells engineered to express immune checkpoint antibodies (CTLA-4 and PD-1) and chimeric antigen receptor targeting MUC1 in adult patients with MUC1 positive, advanced recurrent or refractory malignant solid tumors.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Biological: Anti-CTLA-4/PD-1 expressing MUC1-CAR-T Phase 1 Phase 2

Detailed Description:

This study will be conducted using a phase I/II trial design to assess the safety and efficacy of the CTLA-4 and PD-1 antibodies expressing MUC1-CAR-T for patients with MUC1 positive, advanced recurrent or refractory malignant solid tumors. MUC1-CAR-T can specificly and effectively kill the MUC1 positive cancer cells, CTLA4 and PD-1 antibodies are secreted from the CAR-T cells could improve immunosuppression microenvironment, new CAR-T cells contain the advantages of CAR-T and immune checkpoint inhibitor, which is a promising therapeutic method for advanced solid tumors.

The new CAR-T therapy is applied to clinical practice as bellow. T cells are prepared from peripheral blood mononuclear cells (PBMC) by leukapheresis, and then activated and engineered to express CTLA-4 and PD-1 antibodies and chimeric antigen receptor targeting MUC1. Cells are proliferated in culture and returned to the patients by venous transfusion. A total of 40 patients may be enrolled in the study. The total duration of the study is expected to be approximately 24 months.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Clinical Study of CTLA-4 and PD-1 Antibodies Expressing MUC1-CAR-T Cells for Patients With MUC1 Positive Advanced Solid Tumors
Estimated Study Start Date : June 7, 2017
Estimated Primary Completion Date : January 20, 2019
Estimated Study Completion Date : April 20, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Anti-CTLA-4/PD-1 expressing MUC1-CAR-T
This study have only one arm that is anti-CTLA-4/PD-1 expressing MUC1-CAR-T group. All patients with advanced solid tumor will take part in the screening, who matching all the conditions will be chosen for the treatment using CTLA-4 and PD-1 antibodies expressing MUC1-targeted CAR-T cells. New CAR-T cells are cultured from PBMC and returned to the patients by venous transfusion.
Biological: Anti-CTLA-4/PD-1 expressing MUC1-CAR-T
Every cycle, peripheral blood mononuclear cells (PBMC) are collected on day 0, CAR-T cells are cultured in a GMP standard workshop. Patients are given a three-day regimen of chemotherapy consisting of cyclophosphamide aimed to deplete the lymphocytes before cells infusion. Then the patients will receive an i.v.gtt infusion of CTLA-4 and PD-1 antibodies expressing MUC1 targeted CAR-T cells at (2-5) ×10^7 cells/kg from day 18 to day 19 (±2 days). 2 cycles are regarded as a treatment period.
Other Name: CTLA-4 and PD-1 antibodies expressing MUC1-CAR-T cells




Primary Outcome Measures :
  1. Safety of infusion of autologous CTLA-4 and PD-1 antibodies expressing MUC1-targeted CAR-T cells [ Time Frame: 2 years ]
    Determine the toxicity profile of CTLA4 and PD-1 antibodies expressing MUC1-targeted CAR-T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.


Secondary Outcome Measures :
  1. The efficacy of the treatment using CTLA-4 and PD-1 antibodies expressing MUC1-CAR-T cells for advanced solid tumors [ Time Frame: 2 years ]
    The efficacy of the treatment is assessed according to the response evaluation criteria in solid tumor version 1.1 (RECIST1.1), which is defined as complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD).


Other Outcome Measures:
  1. Progression free survival [ Time Frame: 2 years ]
    Progression free survival is defined as the time from the day in which the patient is enrolled to the date on which tumor progresses or the date on which the patient dies for any cause.

  2. Overall survival [ Time Frame: 2 years ]
    Overall survival is defined as the time from the day in which the patient is enrolled to the date on which the patient dies for any cause.

  3. Change of life quality [ Time Frame: 2 years ]
    Life quality is assessed before and after the treatment.

  4. Proliferation and persistence of MUC1 specific CAR-T cells in peripheral blood of the patients after treatment [ Time Frame: 6 months ]
    CAR-T proportion in peripheral blood of the patients is detected by flow cytometry assay to study the proliferation and persistence of MUC1 specific CAR-T cells.

  5. CTLA-4 and PD-1 antibodies level in peripheral blood of the patients after treatment [ Time Frame: 6 months ]
    CTLA-4 and PD-1 antibodies level are detected by ELISA assay to asess the expressing level of CTLA4 and PD-1 antibodies from CAR-T cells.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with relapsed or refractory advanced solid malignancies (diagnosed by histology or cytology detection).
  2. Progressive disease and no response after at least second-line therapy.
  3. Gender unlimited, age from 18 years to 80 years.
  4. Life expectancy≥3 months.
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  6. Adequate venous access for peripheral blood mononuclear cell (PBMC) apheresis, and no other contraindications.
  7. Immunohistochemistry (IHC) score of MUC1 on tumor tissue ≥1+.
  8. Adequate hepatic function, renal function and bone marrow function (withhin 7 days before enrollment): white blood cell (WBC)≥3.0×10^9/L; platelet≥100×10^9/L; hemoglobin≥90 g/L; lymphocyte ≥0.7×10^9/L; total bilirubin ≤2 times the upper limit of the normal value; alanine aminotransferase and aspartate transaminase (ALT and AST) ≤2.5 times the upper limit of the normal value; serum creatinine ≤1.5 times the upper limit of the normal value.
  9. There is no other treatments (chemotherapy, radiotherapy, etc.) within four weeks before enrollment.
  10. There is at least one measurable tumor lesion.
  11. Patients have adequate ability to understand, sign informed consents and take part in the clinical research voluntarily.
  12. Female patients in child bearing period must have evidence of negative pregnancy test, and agree to take effective contraceptive measures until 4 months after cells infusion.

Exclusion Criteria:

  1. Patients with two or more kinds of tumors.
  2. Patients with active viral or bacterial infection, and have failed to be controlled by anti-infective treatment.
  3. Patients with seropositive reponse of Human immunodeficiency virus (HIV) and syphilis, or fail to control the hepatitis B virus or hepatitis C virus infection.
  4. Patients with active rheumatic diseases, organ transplantation and other diseases affecting the immune system seriously.
  5. Patients with severe heart and lung dysfunction.
  6. Patients with severe chronic diseases of kidney, liver and other important organs.
  7. Patients with any other serious illnesse that the investigators consider it will may affect the patient's treatments, follow-up or assessment, including any uncontrolled clinically significant neurological or psychiatric disorders, immunoregulatory diseases, metabolic diseases, infectious diseases and so on.
  8. Patients who take part in clinical trials of other drugs or biological therapy at present or within 30 days before enrollment.
  9. Patients who need long-term use of immunosuppressive drugs or patients who are undergoing treatment of autoimmune diseases.
  10. Patients who need long-term use of glucocorticoid.
  11. Women patients in gestation period or suckling period.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03179007


Contacts
Layout table for location contacts
Contact: Zhiwei Zhang, Ph.D 0086-021-39595338 zhangzw@shcell.com

Locations
Layout table for location information
China, Zhejiang
Ningbo No.5 Hospital (Ningbo Cancer Hospital) Recruiting
Ningbo, Zhejiang, China, 315201
Contact: Bi Wang    0086-0574-86689113    biwang0217@126.com   
Principal Investigator: Jiangtao Wang         
Sponsors and Collaborators
Shanghai Cell Therapy Research Institute
Investigators
Layout table for investigator information
Study Chair: Qijun Qian, Ph.D Shanghai Cell Therapy Research Institute
Study Chair: Huajun Jin, Ph.D Shanghai Cell Therapy Research Institute
Study Director: Zhiwei Zhang, Ph.D Shanghai Cell Therapy Research Institute
Study Director: Yan Sun Shanghai Cell Therapy Research Institute
Principal Investigator: Jiangtao Wang Ningbo No.5 Hospital(Ningbo Cancer Hospital)

Layout table for additonal information
Responsible Party: Shanghai Cell Therapy Research Institute
ClinicalTrials.gov Identifier: NCT03179007    
Other Study ID Numbers: H2017-04-P01
First Posted: June 7, 2017    Key Record Dates
Last Update Posted: June 7, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Shanghai Cell Therapy Research Institute:
MUC1
CTLA-4
PD-1
chimeric antigen receptor T cells
solid tumor
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms
Antibodies
Immunoglobulins
Immunologic Factors
Physiological Effects of Drugs