Genetically Modified T Cells and Decitabine in Treating Patients With Recurrent or Refractory Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
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|ClinicalTrials.gov Identifier: NCT03017131|
Recruitment Status : Active, not recruiting
First Posted : January 11, 2017
Last Update Posted : June 16, 2020
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma||Biological: Aldesleukin Drug: Cyclophosphamide Drug: Decitabine Biological: Genetically Engineered NY-ESO-1-specific T Lymphocytes Other: Laboratory Biomarker Analysis||Phase 1|
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.
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.
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).
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 (Clinical Trial)|
|Actual Enrollment :||9 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Open Label Clinical Trial Evaluating the Safety and Efficacy of Adoptive Transfer of NY-ESO-1 TCR Engineered Autologous T Cells in Combination With Decitabine in Patients With Recurrent or Treatment Refractory Ovarian Cancer|
|Actual Study Start Date :||December 8, 2017|
|Estimated Primary Completion Date :||December 8, 2020|
|Estimated Study Completion Date :||December 8, 2021|
Experimental: Treatment (decitabine, genetically modified T cells)
COURSE 1: Patients receive decitabine IV daily over 1 hour on days -8 to -6, cyclophosphamide IV over 2 hours on days -4 and -3, and genetically engineered NY-ESO-1-specific T lymphocytes IV and IP on day 0. Patients also receive aldesleukin SC BID on days 1-14..
Biological: Genetically Engineered NY-ESO-1-specific T Lymphocytes
Given IV and IP
Other: Laboratory Biomarker Analysis
- Incidence of adverse events as defined by National Cancer Institute Common Terminology Criteria for Adverse Events version 4 [ Time Frame: Up to 28 days post infusion ]The frequency of toxicities will be tabulated by grade across all dose levels and cycles.
- Appearance of target antigen/major histocompatibility complex loss variants upon disease recurrence [ Time Frame: Up to 15 years ]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.
- Clinical response rates [ Time Frame: Up to 15 years ]Percentage of complete and partial responses and the corresponding 95% confidence interval will be calculated.
- Duration of response [ Time Frame: Up to 15 years ]Will be observed.
- Immunological parameters associated with T cell persistence, bioactivity and functionality [ Time Frame: Up to 15 years ]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.
- Overall survival [ Time Frame: Up to 15 years ]Will be observed.
- Progression free survival [ Time Frame: Up to 15 years ]The median progression free survival and the corresponding 95% confidence interval will be calculated.
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): NCT03017131
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|Principal Investigator:||Kunle Odunsi||Roswell Park Cancer Institute|