Clinical Trial 18350

Cancer Type: Sarcoma
Interventions:MESNA; NY-ESO-1c259T; Neupogen (filgrastim); cyclophosphamide; cytoxan (cyclophosphamide); filgrastim; fludarabine (Fludarabine phosphate)

Study Type: Treatment
Phase of Study: Pilot
Investigators:

  • Mihaela Druta

Overview

Study Title

A Pilot Study of Genetically Engineered NY-ESO-1 Specific NY-ESO-1c259T in HLA-A2+ Patients with Synovial Sarcoma

Summary

The purpose of this early (pilot) clinical trial is to test the effects (both good and bad) of chemotherapy and adoptive immunotherapy with T cells engineered to recognize NY-ESO-1 peptide in patients with unresectable, metastatic or recurrent synovial sarcoma.

Objective

1.1.1 Primary: Determine the safety of treatment with adoptively transferred NY-ESO-1c259T in patients with unresectable, metastatic or recurrent synovial sarcoma. Determine the efficacy through response rate and duration in patients with unresectable, metastatic or recurrent synovial sarcoma treated with lymphodepletion and Treg depletion followed by adoptive immunotherapy with T cells engineered to recognize an HLA-A2 restricted NY-ESO-1 derived peptide, but without aldesleukin. 1.1.2 Secondary: Determine the response rate and duration when patients with low NY-ESO-1 expression are treated with NY-ESO-1c259T. Determine the response rate and duration when NY-ESO-1c259T is administered with a lymphodepletion regimen that does not contain fludarabine. Evaluate persistence and expansion of adoptively transferred NY-ESO-1c259T and correlate with clinical responses. Monitor T-cell subsets in the adoptively transferred cells and in patients treated, and compare clinical outcomes with T-cell subsets levels. When possible, assess whether patients with progressive disease following NY-ESO-1c259T experience a response following a second dose administered with aldesleukin. 1.1.3 Exploratory: Evaluate candidate biomarkers in tumor tissue, including NY-ESO-1 expression, modulation in tumor infiltrating T-cells pre and post-infusion, etc. and correlate with clinical response to treatment. Evaluate candidate biomarkers in blood samples and correlate with clinical response to treatment. Evaluate antigen spreading within the tumor using molecular and immunohistochemical analyses of the diversity of infiltrating T cell clones in pre and post-infusion tumor tissue.

Inclusion Criteria

  • Synovial sarcoma that has been treated with standard chemotherapy containing ifosfamide and/or doxorubicin and remains: unresectable or metastatic or progressive/persistent or recurrent disease
  • Measurable disease
  • Must have proven positive tumor sample for NY-ESO-1
  • HLA-A*0201, HLA-A*0205, and/or HLA-A*0206 by high resolution testing at a local or central laboratory
  • Weigh more than 18 kg
  • All previous cytotoxic chemotherapy, monoclonal antibody therapy, or immune therapy must be washed out 3 weeks before apheresis and must completed at least 3 weeks prior to study entry.
  • Systemic corticosteroid or other immunosuppressive therapy should be washed out 2 weeks before apheresis and must be completed at least 2 weeks prior to pre-infusion lymphodepletive chemotherapy.
  • Biologic or other approved molecular targeted small molecule inhibitors should be washed out 1 week or 5 half-lives (whichever is longer) before apheresis and must be completed at least 1 week or 5 half-lives (whichever is longer) prior to pre-infusion lymphodepletive chemotherapy.
  • Any grade 3 or 4 hematologic toxicity of any previous therapy must have resolved to grade 2 or less prior to apheresis and any grade 3 or 4 toxicity must have resolved to grade 2 or less prior to pre-infusion chemo
  • Eastern Cooperative Oncology Group (ECOG) 0-1, or for children ≤10 years of age, Lansky > 60
  • Life expectancy greater than 3 months
  • Left ventricular ejection fraction ≥ 40% or fractional shortening ≥ 28%
  • T. bilirubin less than 2 mg/dl (Patients with Gilbert Syndrome total bilirubin less than 3xULN and direct bilirubin ≥35%)
  • AST, ALT ≤ 2.5 x upper limit of normal
  • Absolute Neutrophil Count (ANC) ≥ 1.0 x 10^9/L
  • Platelets ≥ 75 x 10^9/L
  • Age-adjusted normal serum creatinine or a creatinine clearance ≥ 40 ml/min
  • Male participants must be willing to practice birth control (including abstinence) during and for 2 months after treatment. Female participants must be willing to practice birth control (including abstinence) during treatment and for 4 months after gene modified cells are no longer detected in body.

  • Exclusion Criteria

  • Clinically significant systemic illness that in the judgment of the Principal Investigator (PI) would compromise the participant's ability to tolerate protocol therapy or significantly increase the risk of complications
  • Untreated Central Nervous System (CNS) metastasis
  • Previous treatment with genetically engineered NY-ESO-1 specific T cells.
  • Females who are pregnant or breastfeeding
  • Active HIV, HBV, HCV or HTLV 1/2 infection infection (due to increased risk of complications during the preparative regimen and confounding effects on the immune system). Active hepatitis B or C infection is defined by seropositive for hepatitis B surface antigen (HbSAg) or hepatitis C antibody with or without elevated liver transaminases.