Clinical Trials /

Phase I/II Study of Anti-Mucin1 (MUC1) CAR T Cells for Patients With MUC1+ Advanced Refractory Solid Tumor

NCT02587689

Description:

The purpose of this study is to determine whether autologous T cells bearing chimeric antigen receptor that can specifically recognize (Mucin 1) MUC1 is safe and effective for patients with relapsed or refractory solid tumor.

Related Conditions:
  • Breast Carcinoma
  • Hepatocellular Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Pancreatic Carcinoma
Recruiting Status:

Unknown status

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase I/II Study of Anti-Mucin1 (MUC1) CAR T Cells for Patients With MUC1+ Advanced Refractory Solid Tumor
  • Official Title: Phase I/II Study of Anti-MUC1 CAR T Cells for Patients With MUC1+ Advanced Refractory Solid Tumor

Clinical Trial IDs

  • ORG STUDY ID: PG-021-001
  • NCT ID: NCT02587689

Conditions

  • Hepatocellular Carcinoma
  • Non-small Cell Lung Cancer
  • Pancreatic Carcinoma
  • Triple-Negative Invasive Breast Carcinoma

Interventions

DrugSynonymsArms
anti-MUC1 CAR T Cellsanti-MUC1-CAR transduced autologous T cellsanti-MUC1 CAR T Cells

Purpose

The purpose of this study is to determine whether autologous T cells bearing chimeric antigen receptor that can specifically recognize (Mucin 1) MUC1 is safe and effective for patients with relapsed or refractory solid tumor.

Trial Arms

NameTypeDescriptionInterventions
anti-MUC1 CAR T CellsExperimentalThe subject's T cells will be modified in one or two different ways that will allow the cells to identify and kill the MUC1+ tumor cells.

    Eligibility Criteria

            Inclusion Criteria:
    
            Male and female subjects with MUC1+ malignancies in patients with no available curative
            treatment options who have limited prognosis (several months to < 2 year survival) with
            currently available therapies will be enrolled:
    
              -  Eligible diseases: MUC1+ hepatocellular carcinoma, non-small cell lung cancer,
                 pancreatic carcinoma and triple-negative basal-like breast carcinoma.
    
                   1. Hepatocellular carcinoma (HCC)
    
                      Clinical diagnosis of HCC was confirmed by histopathological examination of
                      surgical samples in all patients;
    
                   2. Non-small cell lung cancer
    
                      Refractory or recurrent histologically or cytologically confirmed; unresectable;
                      non-squamous NSCLC must have been tested for epidermal growth factor receptor
                      (EGFR) mutation and anaplastic lymphoma kinase (ALK) translocation and if
                      positive should have received appropriate tyrosine kinase inhibitor therapy prior
                      to enrollment;
    
                   3. Pancreatic carcinoma
    
                      Patients with histologic verification of carcinoma of the pancreas (T1-3, N0-1)
                      who have undergone surgical resection within the past 4 - 12 weeks. Patients with
                      R1 resections are excluded;
    
                   4. Triple-negative basal-like breast carcinoma
    
                      Patients with basal-like breast carcinoma must have confirmed triple negative
                      (estrogen receptor negative [ER-]/ progesterone receptor (PR) negative [PR-]/
                      human epidermal growth factor receptor-2 (HER2) negative [HER2-]) .
    
              -  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 18 years of age or older, and must have a life expectancy > 12 weeks.
    
              -  Adequate venous access for apheresis or venous sampling, and no other
                 contraindications for leukapheresis.
    
              -  Females of child-bearing potential must have a negative pregnancy test and all
                 subjects must agree to use an effective method of contraception for up to two weeks
                 after the last infusion of CAR T cells.
    
              -  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.
    
              -  Ability to give informed consent.
    
            Exclusion Criteria:
    
              -  The transduction efficiency of the 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 may not participate.
    
              -  Known HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) 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.
    
              -  Patients need anticoagulant therapy (such as warfarin or heparin).
    
              -  Patients need long-term antiplatelet therapy (aspirin at a dose > 300mg/d; clopidogrel
                 at a dose > 75mg/d).
    
              -  Patients treated by radiotherapy within 4 weeks prior the first apheresis.
    
              -  Patients using fludarabine or cladribine chemotherapy within two years.
          
    Maximum Eligible Age:70 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Phase I: Adverse events attributed to the administration of the anti-MUC1 CAR T cells
    Time Frame:2 years
    Safety Issue:
    Description:

    Details

    Phase:Phase 1/Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:PersonGen BioTherapeutics (Suzhou) Co., Ltd.

    Last Updated

    December 1, 2016