Clinical Trials /

Modified T Cells, Chemotherapy, and Aldesleukin With or Without LV305 and CMB305 in Treating Participants With Advanced or Recurrent Sarcoma

NCT03450122

Description:

This phase I trial studies how well autologous NY-ESO-1-specific CD8-positive T lymphocytes (modified T lymphocytes [T cells]), chemotherapy, and aldesleukin with or without dendritic cell-targeting lentiviral vector ID-LV305 (LV305) and immunotherapeutic combination product CMB305 (CMB305) work in treating participants with sarcoma that has spread to other places in the body (advanced) or that has come back (recurrent). Modified T cells used in this study are taken from participants, are changed in a laboratory, and may "kill" some types of tumor cells. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Cyclophosphamide may help the body get ready to receive the modified T cells. Interleukins, such as aldesleukin, are proteins made by white blood cells and other cells in the body and may help regulate immune response. LV305 and CMB305 may help stimulate the immune system. Giving modified T cells, chemotherapy, aldesleukin, LV305, and CMB305 may work better in treating participants with sarcoma.

Related Conditions:
  • Myxoid Liposarcoma
  • Sarcoma
  • Synovial Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of Adoptive Immunotherapy Using Autologous CD8+ NY-ESO-1-Specific T Cells and the NY-ESO-1 Immunostimulatory Agents LV305 or CMB305 For Patients With Sarcoma
  • Official Title: Phase I Study of Cellular Adoptive Immunotherapy Using Autologous CD8+ NYESO-1-Specific T Cells and the NY-ESO-1 Immunostimulatory Agents LV305 or CMB305 for Patients With Sarcoma

Clinical Trial IDs

  • ORG STUDY ID: 2017-0315
  • SECONDARY ID: NCI-2018-00926
  • SECONDARY ID: 2017-0315
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT03450122

Conditions

  • Malignant Neoplasms of Bone and Articular Cartilage
  • Malignant Neoplasms of Mesothelial and Soft Tissue
  • Synovial Sarcoma
  • Myxoid Liposarcoma
  • HLA-A*0201 Positive Cells Present
  • NY-ESO-1 Positive Tumor Cells Present
  • Recurrent Myxoid Liposarcoma
  • Recurrent Synovial Sarcoma

Interventions

DrugSynonymsArms
Aldesleukin125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2, Recombinant Human Interleukin-2Cohort 0: Modified T Cells
Autologous NY-ESO-1-specific CD8-positive T LymphocytesCohort 0: Modified T Cells
Cyclophosphamide(-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719Cohort 0: Modified T Cells
Dendritic Cell-targeting Lentiviral Vector ID-LV305DCvex-NY-ESO-1, ID-LV305Cohort 0: Modified T Cells
Immunotherapeutic Combination Product CMB305CMB 305, CMB305, ID-CMB305, ID-LV305 Plus ID G305, LV 305 Plus G 305, LV305 Plus G305Cohort 0: Modified T Cells

Purpose

The goal of this clinical research study is to learn if it is safe to give modified, or changed, T cells (called CD8+ NY-ESO-1T cells) alone or in combination with LV305 and CMB305 to patients with sarcoma. Researchers also want to learn if this combination can help to control the disease. T cells are a natural type of immune cell. The changed T cells used in this study will be your own that can be changed in a laboratory and designed to "kill" some types of cancer cells. This is an investigational study. Modified T cell infusions are not commercially available or FDA approved. Additionally, neither LV305 nor CMB305 are FDA approved or commercially available. It is investigational to give the combination of modified T cell infusions, LV305, and CMB305 to sarcoma patients. The study doctor can explain how the study drugs are designed to work. Up to 18 participants will be enrolled in this study. All will take part at MD Anderson.

Detailed Description

      PRIMARY OBJECTIVES:

      I. Evaluate the safety of adoptively transferred CD8 T cells targeting NY-ESO-1 positive (+)
      tumors given alone and in combination with antigen-specific vaccination.

      II. Evaluate the functional and numeric in vivo persistence of NY-ESO-1-specific CD8 T-cells
      given alone and in combination with antigen-specific vaccination.

      SECONDARY OBJECTIVES:

      I. Evaluate the anti-tumor efficacy achieved following adoptive transfer of NY-ESO-specific
      CD8 T cells in combination with LV305 alone and with G305 vaccine in patients with advanced
      synovial and mixed round cell liposarcoma.

      II. Evaluate the influence of antigen-specific vaccination on the induction of both CD8 and
      CD4 T cells to NY-ESO-1 and non-targeted tumor-associated antigens (antigen-spreading) and
      the correlation of these responses with clinical outcome.

      OUTLINE: Participants are assigned to 1 of 3 groups.

      COHORT 0: Participants receive cyclophosphamide intravenously (IV) over 30-60 minutes on day
      -2 and autologous NY-ESO-1-specific CD8-positive T lymphocytes IV over 60 minutes on day 0.
      Then, 6 hours later and twice a day for 14 days, receive aldesleukin subcutaneously (SC) in
      the absence of disease progression or unacceptable toxicity.

      COHORT 1: Participants receive cyclophosphamide, autologous NY-ESO-1-specific CD8-positive T
      lymphocytes, and aldesleukin as in Cohort 0. Participants also receive dendritic
      cell-targeting lentiviral vector ID-LV305 intradermally (ID) on days 1, 22, 43, and 64 in the
      absence of disease progression or unacceptable toxicity.

      COHORT 2: Participants receive cyclophosphamide, autologous NY-ESO-1-specific CD8-positive T
      lymphocytes and aldesleukin as in Cohort 0. Participants also receive dendritic
      cell-targeting lentiviral vector ID-LV305 injection on days 1, 14, 43, and 70, and
      immunotherapeutic combination product CMB305 intramuscularly (IM) on days 29, 57, and 85 in
      the absence of disease progression or unacceptable toxicity.

      After conclusion of study treatment, participants are followed up every 4 weeks for 168 days,
      then every 3 months for 24 months.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 0: Modified T CellsExperimentalRun In Cohort: Participants receive Cyclophosphamide by vein on Day -2. Participants receive a single infusion of NY-ESO-1-specific CTL alone and observed for any signs of toxicity. Low-dose IL-2 given subcutaneously within 6 hours of T cell infusion, then 2 times each day after that for 14 days.
  • Aldesleukin
  • Autologous NY-ESO-1-specific CD8-positive T Lymphocytes
  • Cyclophosphamide
  • Dendritic Cell-targeting Lentiviral Vector ID-LV305
  • Immunotherapeutic Combination Product CMB305
Cohort 1: Modified T Cells + LV305ExperimentalParticipants receive Cyclophosphamide by vein on Day -2. Participants receive modified T cells by vein on Day 0. Low-dose IL-2 given subcutaneously within 6 hours of T cell infusion, then 2 times each day after that for 14 days. Participants receive injections of LV305 on Days 1, 22, 43, and 64.
  • Aldesleukin
  • Autologous NY-ESO-1-specific CD8-positive T Lymphocytes
  • Cyclophosphamide
  • Dendritic Cell-targeting Lentiviral Vector ID-LV305
Cohort 2: Modified T Cells + LV305 + CMB305ExperimentalParticipants receive Cyclophosphamide by vein on Day -2. Participants receive modified T cells by vein on Day 0. Low-dose IL-2 given subcutaneously within 6 hours of T cell infusion, then 2 times each day after that for 14 days. Participants receive injections of LV305 on Days 1, 14, 43, and 70. Participants also receive injections of CMB305 on Days 29, 57, and 85.
  • Aldesleukin
  • Autologous NY-ESO-1-specific CD8-positive T Lymphocytes
  • Cyclophosphamide
  • Dendritic Cell-targeting Lentiviral Vector ID-LV305
  • Immunotherapeutic Combination Product CMB305

Eligibility Criteria

        Inclusion Criteria:

          -  Histopathologic documentation of synovial sarcoma or myxoid liposarcoma with the
             diagnosis of advanced or recurrent disease who have received prior standard
             chemotherapy. Patients with other sarcoma subtypes if proven to be NY-ESO-1 positive
             and meeting all other eligibility criteria listed below will also be included.

          -  Tumor expression of NY-ESO-1 (2+ staining or > 25%) by immunohistochemistry (IHC).

          -  Expression of HLA-A*0201.

          -  Eastern Cooperative Oncology Group (ECOG)/ Zubrod performance status of '0-1'

          -  Life expectancy > 6 months.

          -  Electrocardiography (ECG) without evidence of clinically significant arrhythmia or
             ischemia.

          -  Women of childbearing potential (WOCBP) must be using at least one highly effective or
             two effective accepted methods of contraception to avoid conception throughout the
             study in such a manner that the risk of pregnancy is minimized. Suggested precautions
             should be used to minimize the risk or pregnancy for at least 1 month before start of
             therapy, and while women are on study for up to 3 months after T cell infusion and/or
             at least 3 months after the study agents LV305 or CMB305 are stopped. WOCBP include
             any female who has experienced menarche and who has not undergone successful surgical
             sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is
             not postmenopausal.

          -  Men must be willing and able to use an acceptable method of birth control such as
             latex condom during the dosing period and for at least 3 months after completion of
             the study agent administration (T cell infusion and/or LV305 or CMB305) if their
             sexual partners are WOCBP.

          -  Willing and able to give informed consent.

          -  (Prior to treatment) Note: evaluate at least 1 week before T cell infusion. a.
             Adequate venous access - consider peripherally inserted central catheter (PICC) or
             central line. b. ECOG/Zubrod performance status of '0-1. c. Bi-dimensionally
             measurable disease by palpation on clinical exam, or radiographic imaging (X-ray,
             computed tomography [CT scan]). d. At least 4 weeks must have elapsed since the last
             chemotherapy, immunotherapy, radiotherapy or major surgery. At least 6 weeks for
             nitrosoureas, mitomycin C and liposomal doxorubicin. e. Toxicity related to prior
             therapy must either have returned to =< grade 1, baseline, or been deemed
             irreversible. f. Persons of reproductive potential must agree to use and utilize an
             adequate method of contraception throughout treatment and for at least 3 months after
             study drug is stopped. g. Willing and able to give informed consent.

        Exclusion Criteria:

          -  Patients with active infections or oral temperature > 38.2 Celsius (C) within 72 hours
             of leukapheresis. The procedure may be deferred.

          -  Investigational therapy within 3 weeks.

          -  Prior administration of other NY-ESO-1 targeting immunotherapeutics.

          -  Significant immunosuppression from concurrent, recent (=< 4 weeks ago) or anticipated
             treatment with systemic corticosteroids at any dose, or other immunosuppressive
             medications such as methotrexate, cyclosporine, azathioprine (antihistamines,
             non-steroidal anti-inflammatory drugs and aspirin permitted) or conditions such as
             common variable hypogammaglobulinemia or exposures such as large field radiotherapy.

          -  Cancer therapies, including chemotherapy, radiation, biologic, or kinase inhibitors,
             granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage
             colony-stimulating factor (GM-CSF) within 3 weeks prior.

          -  Psychiatric, other medical illness or other condition that in the opinion of the
             principal investigator (PI) prevents compliance with study procedures or ability to
             provide valid informed consent.

          -  Significant autoimmune disease with the exception of alopecia, vitiligo,
             hypothyroidism or other conditions that have never been clinically active or were
             transient and have completely resolved and require no ongoing therapy.

          -  Myocardial infarction within 6 months of study initiation, active cardiac ischemia or
             New York Heart Association (NYHA) grade III or IV heart failure.

          -  Peripheral blood leukocyte count (white blood cells [WBC]) < 3000/mm^3.

          -  Absolute neutrophil count =< 1500/mm^3.

          -  Platelets < 75000/mm^3.

          -  Hemoglobin < 10 gm/dL.

          -  Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) > 2.5 x upper
             limit of normal (ULN).

          -  Total serum bilirubin > 1.5 x ULN (patients with Gilbert's disease may be included if
             their total bilirubin is =< 3.0 mg/dL).

          -  Creatinine > 1.5 x ULN. If higher check 24hr clearance, if < 50 ml/min then patient
             will be excluded.

          -  INR (prothrombin time ratio) or partial thromboplastin time (PTT) > 1.5 x ULN (Please
             note: patients with hematopoietic cell transplantation (Hct) < 30%, WBC < 2500/mm/^3
             and platelets < 50,000/mm^3 immediately prior to leukapheresis. The procedure may be
             deferred.)

          -  History of other cancer within 3 years (except non-melanoma cutaneous malignancies and
             cervical carcinoma in situ).

          -  Positive screening tests for human immunodeficiency virus (HIV), hepatitis (Hep) B,
             Hep C, active tuberculosis or recent (< 2 week ago) clinically significant infection
             or evidence of active HIV, Hep B, or Hep C. (Note: If positive results are not
             indicative of true active or chronic infection, the patient can be treated.)

          -  Brain metastases considered unstable as: a. without confirmed stability over 60 days
             in patients previously treated with prior surgery or radiation; OR b. associated with
             symptoms and/or findings; OR c. requiring corticosteroids or anticonvulsants in the
             prior 60 days.

          -  Pregnant, planning to become pregnant, or breast feeding.

          -  Known allergy(ies) to any component of CMB305 or LV305.

          -  Men or women of reproductive ability who are unwilling to use effective contraception
             and women of childbearing potential who are unwilling to undergo pregnancy testing
             before and during the study.

          -  Clinically significant pulmonary dysfunction, as determined by medical history and
             physical exam. Patients so identified will undergo pulmonary functions testing and
             those with forced expiratory volume in 1 second (FEV1) < 2.0 L or carbon monoxide
             diffusing capability (DLco) (correlation for hemoglobin [corr for Hgb]) < 75% will be
             excluded.

          -  Significant cardiovascular abnormalities as defined by any one of the following: a.
             congestive heart failure, b. clinically significant hypotension, c. symptoms of
             coronary artery disease, d. presence of cardiac arrhythmias on electrocardiography
             (EKG) requiring drug therapy, e. ejection fraction < 50 % (dobutimine stress echo).

          -  Active and untreated central nervous system (CNS) metastasis.

          -  Autoimmune disease: patients with a history of inflammatory bowel disease are excluded
             from this study, as are patients with a history of autoimmune disease (e.g. systemic
             lupus erythematosus, vasculitis, infiltrating lung disease) whose possible progression
             during treatment would be considered by the investigator to be unacceptable.

          -  Steroids are not permitted 3 days prior to T cell infusion and concurrently during
             therapy.

          -  No prisoners or children will be enrolled on this study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse Events of Adoptively Transferred CD8 T Cells Targeting NY-ESO-1+ Tumors Given Alone and in Combination with Antigen-Specific Vaccination
Time Frame:14 days after the treatment initiation
Safety Issue:
Description:The occurrence and severity of all AEs (including blood chemistries and hematology results) listed and graded according to the NCI CTCAE v.4.03.

Secondary Outcome Measures

Measure:Anti-Tumor Efficacy Achieved Following Adoptive Transfer of NY-ESO-Specific CD8 T Cells in Combination with LV305 Alone and with G305 Vaccine in Patients with Advanced Synovial and Mixed Round Cell Liposarcoma
Time Frame:Assessment performed at 6 and 12 weeks following T cell infusion and then every 3 months until disease progression or intervening therapy for up to 24 months.
Safety Issue:
Description:Radiographic imaging and clinical assessment of residual disease compared with pre-infusion assessment. RECIST criteria assessed. For RECIST criteria, a complete response (CR) defined as total regression of all tumor, a partial response (PR) as 30% or greater decrease in the sum of the longest diameter of target lesions and progressive disease (PD) as 20% increase in the sum of the longest diameter of target lesions.
Measure:Influence of Antigen-Specific Vaccination on the Induction of Both CD8 and CD4 T Cells to NY-ESO-1 and Non-Targeted Tumor-Associated Antigens (antigen-spreading) and the Correlation of These Responses with Clinical Outcome
Time Frame:(baseline sample), on Days +1, +3, +7, and weekly thereafter for the first 12 weeks (until Day 84), then every 4 weeks for the next 12 weeks (until Day 168)
Safety Issue:
Description:Analysis performed on peripheral blood obtained from patients prior to T cell infusion (baseline sample), on Days +1, +3, +7, and weekly thereafter.
Measure:Anti-Tumor Efficacy Achieved Following Adoptive Transfer of NY-ESO-Specific CD8 T Cells in Combination with LV305 Alone and with G305 Vaccine in Patients with Advanced Synovial and Mixed Round Cell Liposarcoma Assessed by irRC.
Time Frame:Assessment performed at 6 and 12 weeks following T cell infusion and then every 3 months until disease progression or intervening therapy for up to 24 months.
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Malignant neoplasms of bone and articular cartilage
  • Malignant neoplasms of mesothelial and soft tissue
  • Synovial sarcoma
  • Myxoid liposarcoma
  • CD8+ antigen specific T cells
  • Cyclophosphamide
  • Cytoxan
  • Neosar
  • IL-2
  • Aldesleukin
  • Interleukin
  • Proleukin
  • LV305
  • ID-LV305
  • CMB305

Last Updated