Clinical Trials /

A Pilot Study of NY-ESO-1ᶜ²⁵⁹T Cells in Subjects With Advanced Myxoid/ Round Cell Liposarcoma

NCT02992743

Description:

This study is for men and women who have a type of sarcoma that has returned after being treated, or that cannot be surgically removed. The specific type of sarcoma is Myxoid / Round Cell Liposarcoma, also known as High Grade Myxoid Liposarcoma. In addition to this disease patients must also have the tissue type HLA-A*02:01, HLA-A*02:05 or HLA-A*02:06, and a sample of tumor tissue must test positive for the NY-ESO-1 protein. The study treatment is made from some of the patient's own white blood cells called T cells. T cells are collected from the patient and sent to a laboratory to be genetically modified, with the aim that they will be able to destroy the cancer cells. Manufacturing the T cells takes about 1 month to complete. The T cells will be given back to the patient by an intravenous infusion. The purpose of this study is to test whether the T cells have an effect on the cancer and to test whether the treatment can be given safely to patients with this disease.

Related Conditions:
  • Myxoid Liposarcoma
  • Round Cell Liposarcoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Pilot Study of NY-ESO-1ᶜ²⁵⁹T Cells in Subjects With Advanced Myxoid/ Round Cell Liposarcoma
  • Official Title: A Pilot Study of NY-ESO-1ᶜ²⁵⁹T Cells in Subjects With Advanced Myxoid/ Round Cell Liposarcoma

Clinical Trial IDs

  • ORG STUDY ID: 208469
  • SECONDARY ID: ADP-0011-007
  • NCT ID: NCT02992743

Conditions

  • Neoplasms

Purpose

This study is for men and women who have a type of sarcoma that has returned after being treated, or that cannot be surgically removed. The specific type of sarcoma is Myxoid / Round Cell Liposarcoma, also known as High Grade Myxoid Liposarcoma. In addition to this disease patients must also have the tissue type HLA-A*02:01, HLA-A*02:05 or HLA-A*02:06, and a sample of tumor tissue must test positive for the NY-ESO-1 protein. The study treatment is made from some of the patient's own white blood cells called T cells. T cells are collected from the patient and sent to a laboratory to be genetically modified, with the aim that they will be able to destroy the cancer cells. Manufacturing the T cells takes about 1 month to complete. The T cells will be given back to the patient by an intravenous infusion. The purpose of this study is to test whether the T cells have an effect on the cancer and to test whether the treatment can be given safely to patients with this disease.

Detailed Description

      This is an open label pilot study of gene modified autologous T cells for the treatment of
      advanced myxoid/ round cell liposarcoma or high-grade myxoid liposarcoma.

      Subjects with the HLA-A*02:01, HLA-A*02:05 and/or HLA-A*02:06 allele, whose tumor expresses
      the NY-ESO-1 antigen and who meet study entry criteria will be eligible for enrollment.
      Following enrollment, subjects will undergo leukapheresis for collection of autologous cells
      for processing and manufacture into the NY-ESO-1ᶜ²⁵⁹T cell investigational product.

      Leukapheresis is performed to obtain cells for the manufacture of autologous NY-ESO-1ᶜ²⁵⁹T
      cells. When the manufactured NY-ESO-1ᶜ²⁵⁹T cells are available, subjects will undergo
      lymphodepleting chemotherapy with cyclophosphamide and fludarabine, followed by a single
      infusion of NY-ESO-1ᶜ²⁵⁹T (transduced cell range: 1 to 8 billion cells) that will be
      administered on Day 1.
    

Trial Arms

NameTypeDescriptionInterventions
Autologous genetically modified T Cells, NY-ESO-1ᶜ²⁵⁹TExperimentalGenetic: Autologous genetically modified T Cells, NY-ESO-1ᶜ²⁵⁹T Cytoreductive chemotherapy followed by infusion with NY-ESO-1(c259) transduced autologous T cells. Subjects will receive one infusion of NY-ESO-1 genetically engineered T cells on Day 1.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Subject (or legally authorized representative) has voluntarily agreed to participate
                 by giving written informed consent in accordance with ICH GCP guidelines and
                 applicable local regulations.
    
              -  Subject has agreed to abide by all protocol required procedures including study
                 related assessments, and management by the treating institution for the duration of
                 the study and long term follow-up.
    
              -  Subject is ≥18 years of age at the time of signing the study informed consent.
    
              -  Subject has a diagnosis of high grade myxoid liposarcoma / myxoid round cell
                 liposarcoma confirmed histologically and by the presence of the reciprocal chromosomal
                 translocation t(12;16)(q13;p11) or t(12; 22) (q13;q12)
    
              -  Subject has advanced (metastatic or inoperable) high grade myxoid liposarcoma / myxoid
                 round cell liposarcoma. Inoperable refers to a tumor lesion in which clear margins
                 cannot be obtained without leading to significant functional compromise
    
              -  Subject has measurable disease according to RECIST v1.1 criteria.
    
              -  Subject must be HLA A*02:01, HLA A*02:05 and/or HLA-A*02:06 positive.
    
              -  Subject's tumor (either the most recent archival specimen or a fresh biopsy) shows
                 positive NY-ESO-1 expression defined as ≥30% of cells that are 2+ or 3+ by
                 immunohistochemistry. All samples must have been pathologically reviewed by an
                 Adaptimmune designated central laboratory.
    
              -  Subject must have previously received or be intolerant to anthracycline based therapy
                 for advanced (metastatic or inoperable) disease. Subjects who received
                 neoadjuvant/adjuvant anthracycline based therapy and progressed within 6 months of
                 completion of therapy will be eligible
    
              -  Subject has an ECOG Performance Status 0-1.
    
              -  Subject has a left ventricular ejection fraction ≥45%.
    
              -  Subject is fit for apheresis and has adequate venous access for the cell collection.
    
              -  Female subjects of childbearing potential (FCBP) must have a negative urine or serum
                 pregnancy test AND must agree to use effective contraception throughout the study,
                 starting at the first dose of chemotherapy for at least 12 months thereafter and 4
                 months after the gene modified cells are no longer detected in the blood, whichever is
                 longer.
    
            Or
    
              -  Male subjects must be surgically sterile or agree to use effective contraception
                 starting at the first dose of chemotherapy and for 4 months thereafter (if indicated
                 in the country specific monograph/label for cyclophosphamide).
    
              -  Subject must have adequate organ function as indicated by the laboratory values below:
    
            Absolute Neutrophil count (ANC) ≥ 1.5 x 10⁹/L (without G-CSF support) Platelets ≥ 100 x
            10⁹/L Hemoglobin ≥ 80 g/L (without transfusion support within 7 days prior to
            leukapheresis) Prothrombin Time or INR ≤ 1.5x upper limit of normal (ULN) unless receiving
            therapeutic anticoagulation.
    
            Partial Thromboplastin Time (PTT) ≤ 1.5x upper limit of normal (ULN) unless receiving
            therapeutic anticoagulation.
    
            Calculated or measured creatinine clearance ≥ 40 mL/min Serum total bilirubin ≤ 1.5 x ULN
            (unless subject has documented Gilbert's Syndrome with direct bilirubin <35% of total
            bilirubin) Alanine aminotransferase (ALT)/Serum Glutamic Pyruvic Transaminase (SGPT) ≤ 2.5x
            ULN
    
            Exclusion Criteria:
    
              1. Subject has received or plans to receive the following therapy/treatment within the
                 following periods prior to leukapheresis or lymphodepleting chemotherapy:
    
                   -  Cytotoxic chemotherapy within 4 weeks.
    
                   -  Immune therapy (monoclonal antibody therapy, checkpoint inhibitors) within 4
                      weeks.
    
                   -  Use of an anti-cancer vaccine within 2 months in the absence of tumor response,
                      or the subject should be excluded if their disease is responding to an
                      experimental vaccine given within 6 months.
    
                   -  Any previous gene therapy using an integrating vector.
    
                   -  Corticosteroids or any other immunosuppressive therapy within 2 weeks. Use of
                      inhaled or topical cutaneous steroids is permitted.
    
                   -  Any previous allogeneic hematopoietic stem cell transplant.
    
                   -  Investigational treatment or clinical trial within 4 weeks.
    
              2. Radiotherapy to the target lesions within 3 months prior lymphodepleting chemotherapy.
                 A lesion with unequivocal progression may be considered a target lesion. There is no
                 washout period for palliative radiation to non-target lesions.
    
              3. Subject that has toxicity from previous anti-cancer therapy must have recovered to ≤
                 Grade 1 (except for non-clinically significant toxicities, e.g., alopecia, vitiligo).
                 Subjects with Grade 2 toxicities that are deemed stable or irreversible (e.g.
                 peripheral neuropathy) can be enrolled.
    
              4. Subject has history of allergic reactions attributed to compounds of similar chemical
                 or biologic composition to fludarabine, cyclophosphamide or other agents used in the
                 study.
    
              5. Subject has history of chronic or recurrent (within the last year prior to screening)
                 severe autoimmune or immune mediated disease requiring steroids or other
                 immunosuppressive treatments.
    
              6. Subject has known active brain or leptomeningeal metastases. Subjects with prior
                 history of brain metastasis who have undergone local therapy (i.e. metastatectomy
                 and/or radiation) and show no evidence of local recurrence or progression over the
                 past 3 months prior to screening are eligible.
    
              7. Subject has other prior malignancy that is not in complete remission.
    
              8. Subject has electrocardiogram (ECG) showing clinically significant abnormality at
                 screening or an average QTc interval (Fridercia's or Bazett's formula) >450 msec in
                 males and >470 msec in females (>480 msec for subjects with Bundle Branch Block
                 (BBB)).
    
              9. Subject has uncontrolled intercurrent illness including, but not limited to:
    
                   -  Ongoing or active infection.
    
                   -  Clinically significant cardiac disease defined by congestive heart failure New
                      York Heart Association (NYHA) Class 3 or Class 4.
    
                   -  Uncontrolled clinically significant arrhythmia in last 6 months.
    
                   -  Acute Coronary Syndrome (ACS) (angina or MI) in last 6 months.
    
                   -  Interstitial lung disease (subjects with existing pneumonitis as a result of
                      radiation are not excluded, however, subjects must not be oxygen dependent).
    
             10. Subjects who in the opinion of the Investigator will be unlikely to fully comply with
                 protocol requirements.
    
             11. Subject has active infection with HIV, HBV, HCV or HTLV as defined below:
    
                   -  Positive serology for HIV
    
                   -  Active hepatitis B infection as demonstrated by test for hepatitis B surface
                      antigen. Subjects who are hepatitis B surface antigen negative but are hepatitis
                      B core antibody positive must have undetectable hepatitis B DNA and receive
                      prophylaxis against viral reactivation.
    
                   -  Active hepatitis C infection as demonstrated by test for hepatitis C RNA.
                      Subjects who are HCV antibody positive will be screened for HCV RNA by any RT PCR
                      or bDNA assay. If HCV antibody is positive, eligibility will be determined based
                      on a negative screening RNA value.
    
                   -  Positive serology for HTLV 1 or 2.
    
             12. Subject is pregnant or breastfeeding.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Proportion of subjects with a confirmed Complete Response (CR) or Partial Response (PR).
    Time Frame:1 Year
    Safety Issue:
    Description:Evaluation of the efficacy of the treatment by assessment of the Overall Response Rate according to RECIST v1.1.

    Secondary Outcome Measures

    Measure:Interval between the date of first T cell infusion dose and first documented evidence of CR or PR.
    Time Frame:1 Year
    Safety Issue:
    Description:Evaluation of the efficacy of the treatment by assessment of time to first response.
    Measure:Interval between the date of first documented evidence of CR or PR until first documented disease progression or death due to any cause.
    Time Frame:1 Year
    Safety Issue:
    Description:Evaluation of the efficacy of the treatment by assessment of duration of response.
    Measure:Interval between the date of first documented evidence of SD until first documented disease progression or death due to any cause.
    Time Frame:1 Year
    Safety Issue:
    Description:Evaluation of the efficacy of the treatment by assessment of duration of stable disease.
    Measure:Interval between the date of first T cell infusion and the earliest date of disease progression or death due to any cause.
    Time Frame:1 Year
    Safety Issue:
    Description:Evaluation of the efficacy of the treatment by assessment of progression-free survival.
    Measure:Interval between the date of first T cell infusion and date of death due to any cause.
    Time Frame:1 Year
    Safety Issue:
    Description:Evaluation of the efficacy of the treatment by assessment of overall survival.
    Measure:Number of subjects with adverse events (AE), including serious adverse events (SAE).
    Time Frame:1 Year
    Safety Issue:
    Description:Determine if treatment with autologous genetically modified T cells (NY-ESO-1ᶜ²⁵⁹T) is safe and tolerable through laboratory assessments, including chemistry and hematology, and anti-NY-ESO-1 antibodies; and cardiac assessments, including ECG.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:GlaxoSmithKline

    Trial Keywords

    • Previously treated
    • Metastatic
    • Cell Therapy
    • T Cell Therapy
    • Sarcoma
    • NY-ESO-1
    • Immuno-oncology
    • T Cell Receptor

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