Clinical Trials /

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

NCT03450122

Description:

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.

Related Conditions:
  • Myxoid Liposarcoma
  • 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+ NY-ESO-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
  • NCT ID: NCT03450122

Conditions

  • Malignant Neoplasms of Bone and Articular Cartilage
  • Malignant Neoplasms of Mesothelial and Soft Tissue
  • Synovial Sarcoma
  • Myxoid Liposarcoma

Interventions

DrugSynonymsArms
Modified T CellsCohort 0: Modified T Cells
CyclophosphamideCytoxan, NeosarCohort 0: Modified T Cells
IL-2Aldesleukin, Interleukin, ProleukinCohort 0: Modified T Cells
LV305ID-LV305Cohort 1: Modified T Cells + LV305
CMB305Cohort 2: Modified T Cells + LV305 + CMB305

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 participant's 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

      Leukapheresis (Apheresis):

      If participant is found to be eligible to take part in this study, some of participant's
      blood cells will be collected by leukapheresis. For this procedure, participant will need to
      stay seated in a chair and keep both arms still for up to 4 hours. During this process,
      participant's blood will flow into the machine and then directly back into participant's
      bloodstream through the second line. Blood will be drawn from 1 arm through a catheter
      (needle and tube) connected to the leukapheresis machine. Inside the machine, the white blood
      cells will be separated from the rest of the blood cells and collected in a sterile bag.
      Then, the rest of the blood cells will be returned through a catheter to your other arm. A
      blood thinner called citrate will be added to the blood as it enters the machine in order to
      lower the risk of participant's blood clotting in the machine.

      If participant cannot tolerate the leukapheresis procedure, this blood may be drawn by vein
      (like a regular blood draw).

      Researchers may also used white blood cells previously collected from participant when and if
      participant consented to take part in protocol PA14-0138.

      The blood will be sent to the laboratory where the T cells will be grown. It will take about
      6-8 weeks for participant's T cells to grow in the laboratory.

      It is possible that participant will need to have a central venous catheter (CVC) placed for
      this procedure. A CVC is a sterile flexible tube that will be placed into a large vein while
      participant is under local anesthesia. Participant's doctor will explain this procedure to
      participant in more detail, and participant will be required to sign a separate consent form.

      It is possible that participant's T cells may not grow and then cannot be infused back into
      participant. If this happens with participant's cells, the study doctor will talk to
      participant about options available to participant. One option may be that participant will
      have another leukapheresis procedure done and another attempt is made to make the changed T
      cells.

      Study Groups:

      Participant will be assigned to a study group (also called a Cohort) depending on when
      participant enrolls in this study:

        -  If participant is in Cohort 0, participant will receive modified T cells.

        -  If participant is in Cohort 1, participant will receive modified T cells and LV305.

        -  If participant is in Cohort 2, participant will receive modified T cells, LV305, and
           CMB305.

      Study Drug and T cell Administration:

      Participant will have 1 infusion of chemotherapy (cyclophosphamide) before participant
      receives participant's changed T cells. The chemotherapy will help participant's body get
      ready to receive participant's changed T cells.

      Negative days are the days before participant receives the T cells and positive days are the
      days after participant receives the T cells. Day 0 is the day participant receives the T
      cells.

      On Day -2, participant will receive cyclophosphamide by vein over about 30-60 minutes.

      On Day 0, participant will receive the modified T cells by vein over about 60 minutes.
      Participant will be admitted to the hospital for the infusion, and participant's study doctor
      will tell participant for how many days participant will remain in the hospital after
      participant receives the changed T cells. Participant will be watched closely for 24 hours
      after participant's T cell infusion to check for any reactions.

      Starting within 6 hours after the modified T cell infusion and then 2 times each day after
      that for 14 days, participant will receive aldesleukin as an injection into participant's
      skin around participant's abdomen. Participant will be taught how to give these injections.

      If participant is in Cohort 1, participant will receive injections of LV305 on Days 1, 22,
      43, and 64.

      If participant is in Cohort 2, participant will receive injections of LV305 on Days 1, 14,
      43, and 70. Participant will also receive injections of CMB305 on Days 29, 57, and 85.

      Participant will also be given standard drugs to help decrease the risk of side effects.
      Participant may ask the study staff for information about how the drugs are given and their
      risks.

      Length of Study:

      Participant will receive the T cells 1 time. If participant is in Cohort 1 or 2, participant
      may receive injections of study drug for up to 85 days after the T cell infusion. Participant
      will have study visits for up to 168 days after the T cell infusion.

      Participant will be taken off study if the disease gets worse, if intolerable side effects
      occur, or if participant is unable to follow study directions.

      Study Visits:

      Within 2 weeks before you receive the T cells:

        -  Participant will have a physical exam.

        -  Blood (about 5 1/2 tablespoons) will be drawn for will be drawn for routine tests,
           immune system tests, and tests on how long the T-cells survive in participant's body.
           This routine blood draw will include a pregnancy test if participant can become
           pregnant.

        -  Participant will have a CT scan to check the status of the disease.

      On Day 0:

        -  Participant will have an EKG before the infusion.

        -  Participant will have a physical exam before the infusion.

        -  Blood (about 5 1/2 tablespoons) will be drawn for will be drawn for routine tests,
           immune system tests, and tests on how long the T-cells survive in participant's body.

      On Days 1 and 3, blood (about 5 1/2 tablespoons) will be drawn for will be drawn for routine
      tests, immune system tests, and tests on how long the T-cells survive in participant's body.

      Beginning with Day 7, participant will have study visits every week for the first 12 weeks
      (until Day 84), then every 4 weeks for the next 12 weeks (until Day 168). At these visits:

        -  Participant will have a physical exam.

        -  Blood (about 5½ tablespoons) will be drawn for routine tests, immune system tests, and
           tests on how long the T-cells survive in participant's body.

        -  Between Day 35 and 42 and again between Day 77 and 84, participant will have a CT scan
           to check the status of the disease.

      If the doctor thinks it is needed, participant will return to the clinic every 8 weeks after
      the last visit or as often as the doctor thinks is needed. Blood (about 5½ tablespoons) will
      be drawn for routine tests, immune system tests, and tests on how long the T-cells survive in
      participant's body.

      Blood (about 5 1/2 tablespoons) will be drawn every 3 months for routine tests, immune system
      tests, and tests on how long the T-cells survive in participant's body and a CT scan will be
      done to check the status of the disease, for up to 24 months after the end of treatment,
      unless the disease gets worse or participant begins a new treatment.
    

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.
  • Cyclophosphamide
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.
  • Cyclophosphamide
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.
  • Cyclophosphamide

Eligibility Criteria

        Inclusion Criteria:

          1. Histopathologic documentation of synovial sarcoma or myxoid liposarcoma with the
             diagnosis of advanced or recurrent disease.

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

          3. Male or female subjects >/= 18 years of age.

          4. Expression of HLA-A*0201

          5. ECOG/ Zubrod performance status of '0-1'

          6. Life expectancy > 6 months

          7. ECG without evidence of clinically significant arrhythmia or ischemia

          8. 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

          9. 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.

         10. Willing and able to give informed consent.

         11. (Prior to treatment) Note: evaluate at least 1 week before T cell infusion. a.
             Adequate venous access - consider 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, 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:

          1. Patients with active infections or oral temperature > 38.2 C within 72 hours of
             Leukapheresis. The procedure may be deferred.

          2. Investigational therapy within 3 weeks

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

          4. 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

          5. Cancer therapies, including chemotherapy, radiation, biologic, or kinase inhibitors,
             G-CSF, GM-CSF within 4 weeks prior

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

          7. 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

          8. Myocardial infarction within 6 months of study initiation, active cardiac ischemia or
             NYHA Grade III or IV heart failure

          9. Inadequate organ function including: a. Marrow: Peripheral blood leukocyte count (WBC)
             < 3000/mm^3, absolute neutrophil count </= 1500/mm^3, platelets < 75000/mm^3, or
             hemoglobin < 10 gm/dL b. Hepatic: Alanine aminotransferase (ALT), and aspartate
             aminotransferase (AST) > 2.5 x 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) c. Renal:
             Creatinine > 1.5 x ULN d. Other: INR (prothrombin time ratio) or partial
             thromboplastin time (PTT) > 1.5 x ULN (Please Note: Patients with Hct < 30%, WBC
             <2500/mm/^3and platelets <50,000/mm^3 immediately prior to Leukapheresis. The
             procedure may be deferred.)

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

         11. Positive screening tests for HIV, 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.)

         12. 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

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

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

         15. Any other malignancy from which the patient has been disease-free for less than 5
             years, with the exception of adequately treated and cured basal or squamous cell skin
             cancer, superficial bladder cancer, carcinoma in situ of the cervix.

         16. 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.

         17. Clinically significant pulmonary dysfunction, as determined by medical history and
             physical exam. Patients so identified will undergo pulmonary functions testing and
             those with FEV1 < 2.0 L or DLco (corr for Hgb) < 75% will be excluded.

         18. 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 EKG requiring drug
             therapy, e. Ejection fraction < 50 % (echocardiogram or MUGA).

         19. Active and untreated central nervous system (CNS) metastasis (including metastasis
             identified during screening MRI or contrast CT).

         20. 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.

         21. Positive screening tests for HIV, Hep B, and Hep C. If positive results are not
             indicative of true active or chronic infection, the patient can be treated.

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

         23. 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:Not yet 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

April 11, 2018