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
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.
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.
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.
- 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
- 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
- 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.
- 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
- 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
- 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
- No prisoners or children will be enrolled on this study.