This phase I trial studies the side effects of genetically modified T cells and decitabine in treating patients with recurrent or refractory epithelial or non-epithelial ovarian, primary peritoneal, or fallopian tube cancer that has come back or has not responded to previous treatments. White blood cells called T cells are collected via a process called leukapheresis, genetically modified to recognize and attack tumor cells, then given back to the patient. Decitabine may induce and increase the amount of the target protein NY-ESO-1 available on the surface of tumor cells. Giving genetically modified T cells and decitabine may kill more tumor cells.
PRIMARY OBJECTIVES: I. To determine the safety and tolerability of the autologous NY-ESO-1 redirected T cell therapy in combination with decitabine and low-dose IL-2 in patients with treatment refractory or recurrent epithelial or non-epithelial ovarian, primary peritoneal or fallopian tube carcinoma. SECONDARY OBJECTIVES: I. To evaluate the persistence of genetically modified cells in the peripheral blood, and at tumor sites. II. To examine the effect of the treatment on tumor as measured by objective tumor response and progression free survival, both assessed by immune-related Response Evaluation Criteria in Solid Tumors (irRECIST). III. To assess the occurrence of target antigen and/or major histocompatibality complex (MHC) loss variants upon disease recurrence. TERTIARY OBJECTIVES: I. To evaluate the post treatment phenotype and functionality of genetically modified T cells isolated from peripheral blood and from tumor sites. II. To assess changes in immunoscore, Tregs, Myeloid cell subsets, and antigen spreading in peripheral blood and tumor site. III. To assess the influence of demographic and disease molecular characteristics on treatment outcomes of complete response (CR) and overall survival (OS). OUTLINE: COURSE 1: Patients receive decitabine IV daily over 1 hour on days -8 to Day -6, cyclophosphamide IV over 2 hours on days -4 and -3, and genetically engineered NY-ESO-1-specific T lymphocytes IV and intraperitoneally (IP) on day 0. Followed by low-dose IL-2 for 2 weeks from Day 1 to Day 14.. After completion of study treatment, patients are followed up monthly at 3-9 months, every 6 months for 4 years, and then annually for up to 15 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
Given SC
Given IV
Given IV
Given IV and IP
Correlative studies
Roswell Park Cancer Institute
Buffalo, New York, United States
Incidence of adverse events as defined by National Cancer Institute Common Terminology Criteria for Adverse Events version 4
The frequency of toxicities will be tabulated by grade across all dose levels and cycles.
Time frame: Up to 28 days post infusion
Appearance of target antigen/major histocompatibility complex loss variants upon disease recurrence
Will be evaluated by quantifying expression of targeted antigens/major histocompatibility complex alleles (NY-ESO-1/human leukocyte antigen-A\*02) in tumor samples obtained on disease recurrence if available, and comparing those values to the pretreatment (diagnosis) samples. NY-ESO-1 expression will be evaluated by quantitative real time polymerase chain reaction immunohistochemistry. Human leukocyte antigen-A\*0201 expression on samples will be evaluated by immunohistochemistry.
Time frame: Up to 15 years
Clinical response rates
Percentage of complete and partial responses and the corresponding 95% confidence interval will be calculated.
Time frame: Up to 15 years
Duration of response
Will be observed.
Time frame: Up to 15 years
Immunological parameters associated with T cell persistence, bioactivity and functionality
Will measure the pre- and post-treatment percentage of transgenic T cells in the peripheral blood, selective migration into the tumor sites, the ex-vivo immune functionality and phenotype of these cells, the modulation of cytokine milieu in serum post treatment as compared to baseline as well as the development of an expanded patient immune response against tumor via epitope spreading.
Time frame: Up to 15 years
Overall survival
Will be observed.
Time frame: Up to 15 years
Progression free survival
The median progression free survival and the corresponding 95% confidence interval will be calculated.
Time frame: Up to 15 years
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