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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03450122
Recruitment Status : Active, not recruiting
First Posted : March 1, 2018
Last Update Posted : September 6, 2019
Sponsor:
Collaborators:
Immune Design
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
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 Biological: Aldesleukin Biological: Autologous NY-ESO-1-specific CD8-positive T Lymphocytes Drug: Cyclophosphamide Biological: Dendritic Cell-targeting Lentiviral Vector ID-LV305 Drug: Immunotherapeutic Combination Product CMB305 Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 13, 2018
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2019


Arm Intervention/treatment
Experimental: Cohort 0: Modified T Cells

Run 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.

Biological: Aldesleukin
Given SC
Other Names:
  • 125-L-Serine-2-133-interleukin 2
  • Proleukin
  • r-serHuIL-2
  • Recombinant Human IL-2
  • Recombinant Human Interleukin-2

Biological: Autologous NY-ESO-1-specific CD8-positive T Lymphocytes
Given by vein

Drug: Cyclophosphamide
Given by vein
Other Names:
  • (-)-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- 138719

Biological: Dendritic Cell-targeting Lentiviral Vector ID-LV305
Given ID
Other Names:
  • DCvex-NY-ESO-1
  • ID-LV305

Drug: Immunotherapeutic Combination Product CMB305
Given IM
Other Names:
  • CMB 305
  • CMB305
  • ID-CMB305
  • ID-LV305 Plus ID G305
  • LV 305 Plus G 305
  • LV305 Plus G305

Experimental: Cohort 1: Modified T Cells + LV305

Participants 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.

Biological: Aldesleukin
Given SC
Other Names:
  • 125-L-Serine-2-133-interleukin 2
  • Proleukin
  • r-serHuIL-2
  • Recombinant Human IL-2
  • Recombinant Human Interleukin-2

Biological: Autologous NY-ESO-1-specific CD8-positive T Lymphocytes
Given by vein

Drug: Cyclophosphamide
Given by vein
Other Names:
  • (-)-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- 138719

Biological: Dendritic Cell-targeting Lentiviral Vector ID-LV305
Given ID
Other Names:
  • DCvex-NY-ESO-1
  • ID-LV305

Experimental: Cohort 2: Modified T Cells + LV305 + CMB305

Participants 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.

Biological: Aldesleukin
Given SC
Other Names:
  • 125-L-Serine-2-133-interleukin 2
  • Proleukin
  • r-serHuIL-2
  • Recombinant Human IL-2
  • Recombinant Human Interleukin-2

Biological: Autologous NY-ESO-1-specific CD8-positive T Lymphocytes
Given by vein

Drug: Cyclophosphamide
Given by vein
Other Names:
  • (-)-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- 138719

Biological: Dendritic Cell-targeting Lentiviral Vector ID-LV305
Given ID
Other Names:
  • DCvex-NY-ESO-1
  • ID-LV305

Drug: Immunotherapeutic Combination Product CMB305
Given IM
Other Names:
  • CMB 305
  • CMB305
  • ID-CMB305
  • ID-LV305 Plus ID G305
  • LV 305 Plus G 305
  • LV305 Plus G305




Primary Outcome Measures :
  1. 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 ]
    The occurrence and severity of all AEs (including blood chemistries and hematology results) listed and graded according to the NCI CTCAE v.4.03.

  2. Functional Persistence of NY-ESO-1-Specific CD8 T-Cells Given Alone and in Combination with Antigen-Specific Vaccination [ Time Frame: Baseline up to Day 168 ]
    The functional persistence of transferred CD8 T cells performed on peripheral blood obtained from patients prior to T cell infusion (baseline sample), on Days +1, +3, +7, and weekly thereafter.

  3. Numeric In Vivo Persistence of NY-ESO-1-Specific CD8 T-Cells Given Alone and in Combination with Antigen-Specific Vaccination [ Time Frame: Baseline up to Day 168 ]
    The numeric persistence of transferred CD8 T cells performed on peripheral blood obtained from patients prior to T cell infusion (baseline sample), on Days +1, +3, +7, and weekly thereafter.


Secondary Outcome Measures :
  1. 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. ]
    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.

  2. 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) ]
    Analysis performed on peripheral blood obtained from patients prior to T cell infusion (baseline sample), on Days +1, +3, +7, and weekly thereafter.

  3. 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. ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03450122


Locations
Layout table for location information
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Immune Design
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Neeta Somaiah M.D. Anderson Cancer Center

Additional Information:
Layout table for additonal information
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03450122     History of Changes
Other Study ID Numbers: 2017-0315
NCI-2018-00926 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2017-0315 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: March 1, 2018    Key Record Dates
Last Update Posted: September 6, 2019
Last Verified: September 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by M.D. Anderson Cancer Center:
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
Additional relevant MeSH terms:
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Sarcoma
Liposarcoma
Sarcoma, Synovial
Liposarcoma, Myxoid
Bone Neoplasms
Soft Tissue Neoplasms
Neoplasms, Fibrous Tissue
Cartilage Diseases
Neoplasms
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms, Adipose Tissue
Neoplasms, Connective Tissue
Neoplasms by Site
Bone Diseases
Musculoskeletal Diseases
Connective Tissue Diseases
Aldesleukin
Cyclophosphamide
Interleukin-2
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Analgesics, Non-Narcotic