Modified T Cells, Chemotherapy, and Aldesleukin With or Without LV305 and CMB305 in Treating Participants With Advanced or Recurrent Sarcoma
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
2 other identifiers
interventional
15
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Sep 2018
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 19, 2018
CompletedFirst Posted
Study publicly available on registry
March 1, 2018
CompletedStudy Start
First participant enrolled
September 13, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 6, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
December 6, 2022
CompletedOctober 16, 2023
October 1, 2023
4.2 years
February 19, 2018
October 13, 2023
Conditions
Outcome Measures
Primary Outcomes (3)
Duration of in vivo persistence of transferred T cells
Will be assessed alone or in combination with dendritic cell-targeting lentiviral vector ID-LV305 (LV305) or in combination with CMB305.
Up to 168 days
The nature, frequency and severity of adverse events
n subjects receiving NY-ESO-1-specific T cells alone, T cells with LV305 and T cells with CMB305
Up to 168 days
The Laboratory abnormalities
Will be assessed in subjects receiving NY-ESO-1-specific T cells alone, T cells with LV305 and T cells with CMB305
Up to 168 days
Secondary Outcomes (4)
Tumor response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and RECIST-based immune-related response (irRC) data
Up to 168 days
Persistence of cellular immune response
Up to 168 days
Differentiation phenotype
Up to 168 days
Antigen-spreading
Up to 168 days
Study Arms (2)
Cohort 0 (cyclophosphamide, T cells, aldesleukin)
EXPERIMENTALParticipants receive cyclophosphamide 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 SC in the absence of disease progression or unacceptable toxicity.
Cohort 1 (cyclophosphamide, T cells, aldesleukin, LV305)
EXPERIMENTALParticipants 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 ID on days 1, 22, 43, and 64 in the absence of disease progression or unacceptable toxicity.
Interventions
Given SC
Given IV
Given IV
Given ID
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- +13 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Neeta Somaiah
M.D. Anderson Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 19, 2018
First Posted
March 1, 2018
Study Start
September 13, 2018
Primary Completion
December 6, 2022
Study Completion
December 6, 2022
Last Updated
October 16, 2023
Record last verified: 2023-10