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

HLA-A*0201 Positive Cells Present Clinical Trial

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

Status Completed

Clinical Trial 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.

Clinical Trial 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.

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

Related Conditions & MeSH terms

• HLA-A*0201 Positive Cells Present
• Liposarcoma
• Liposarcoma, Myxoid
• NY-ESO-1 Positive Tumor Cells Present
• Recurrence
• Recurrent Myxoid Liposarcoma
• Recurrent Synovial Sarcoma
• Sarcoma
• Sarcoma, Synovial

• NCT number: NCT03450122
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Status: Completed
• Phase: Phase 1
• Start date: September 13, 2018
• Completion date: December 6, 2022