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

NCT03179007 | Unknown Phase 1

• 1 other identifier: H2017-04-P01
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced Solid Tumor

Keywords

MUC1; CTLA-4; PD-1; chimeric antigen receptor T cells; solid tumor

Outcome Measures

Primary Outcomes (1)

• Safety of infusion of autologous CTLA-4 and PD-1 antibodies expressing MUC1-targeted CAR-T cells

  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.

  2 years

Secondary Outcomes (1)

• The efficacy of the treatment using CTLA-4 and PD-1 antibodies expressing MUC1-CAR-T cells for advanced solid tumors

  2 years

Other Outcomes (5)

• Progression free survival

  2 years

• Overall survival

  2 years

• Change of life quality

  2 years

Study Arms (1)

Anti-CTLA-4/PD-1 expressing MUC1-CAR-T

EXPERIMENTAL

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

Interventions

Anti-CTLA-4/PD-1 expressing MUC1-CAR-T BIOLOGICAL

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.

Also known as: CTLA-4 and PD-1 antibodies expressing MUC1-CAR-T cells

Anti-CTLA-4/PD-1 expressing MUC1-CAR-T

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with relapsed or refractory advanced solid malignancies (diagnosed by histology or cytology detection).
• Progressive disease and no response after at least second-line therapy.
• Gender unlimited, age from 18 years to 80 years.
• Life expectancy≥3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Adequate venous access for peripheral blood mononuclear cell (PBMC) apheresis, and no other contraindications.
• Immunohistochemistry (IHC) score of MUC1 on tumor tissue ≥1+.
• 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.
• There is no other treatments (chemotherapy, radiotherapy, etc.) within four weeks before enrollment.
• There is at least one measurable tumor lesion.
• Patients have adequate ability to understand, sign informed consents and take part in the clinical research voluntarily.
• 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.

You may not qualify if:

• Patients with two or more kinds of tumors.
• Patients with active viral or bacterial infection, and have failed to be controlled by anti-infective treatment.
• Patients with seropositive reponse of Human immunodeficiency virus (HIV) and syphilis, or fail to control the hepatitis B virus or hepatitis C virus infection.
• Patients with active rheumatic diseases, organ transplantation and other diseases affecting the immune system seriously.
• Patients with severe heart and lung dysfunction.
• Patients with severe chronic diseases of kidney, liver and other important organs.
• 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.
• Patients who take part in clinical trials of other drugs or biological therapy at present or within 30 days before enrollment.
• Patients who need long-term use of immunosuppressive drugs or patients who are undergoing treatment of autoimmune diseases.
• Patients who need long-term use of glucocorticoid.
• Women patients in gestation period or suckling period.

Sponsors & Collaborators

• Shanghai Cell Therapy Research Institute: lead

Study Sites (1)

Ningbo No.5 Hospital (Ningbo Cancer Hospital)

Ningbo, Zhejiang, 315201, China

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Insulin-Dependent, 12

Interventions

CTLA-4 Antigen

Intervention Hierarchy (Ancestors)

Immune Checkpoint Proteins; Proteins; Amino Acids, Peptides, and Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers

Study Officials

• Qijun Qian, Ph.D

  Shanghai Cell Therapy Research Institute

  STUDY CHAIR

• Huajun Jin, Ph.D

  Shanghai Cell Therapy Research Institute

  STUDY CHAIR

• Zhiwei Zhang, Ph.D

  Shanghai Cell Therapy Research Institute

  STUDY DIRECTOR

• Yan Sun

  Shanghai Cell Therapy Research Institute

  STUDY DIRECTOR

• Jiangtao Wang

  Ningbo No.5 Hospital(Ningbo Cancer Hospital)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhiwei Zhang, Ph.D

CONTACT

0086-021-39595338; zhangzw@shcell.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2017
• First Posted: June 7, 2017
• Study Start: June 7, 2017
• Primary Completion: January 20, 2019
• Study Completion: April 20, 2019
• Last Updated: June 7, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)