NY-ESO-1ᶜ²⁵⁹T for Advanced NSCLC
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|ClinicalTrials.gov Identifier: NCT02588612|
Recruitment Status : Active, not recruiting
First Posted : October 28, 2015
Last Update Posted : April 11, 2018
This study is intended for men and women at least 18 years of age who have advanced lung cancer which has grown or returned after being treated. In particular, it is a study for subjects who have a blood test positive for HLA-A*0201, HLA-A*205 and/or HLA-A*0206 protein and a tumor test positive for NY-ESO-1 expression (protein or gene). The study will take the subject's T cells, which are a natural type of immune cell in the blood, and send them to a laboratory to be modified. The changed T cells used in this study will be the subject's own T cells that have been genetically changed with the aim of attacking and destroying cancer cells.
The manufacturing of T cells takes about 1 month to complete. The T cells will be given back to the subject through an intravenous infusion. The purpose of this study is to test the safety of genetically changed T cells and find out what effects, if any, they have in subjects with lung cancer.
Subjects will be seen frequently by the Study Physician right after receiving their T cells back. Subjects will then be entered into a long-term follow up in order to monitor the subject. Subjects will be seen every 6 months by their Study Physician for the first 5 years after the T cell infusion. If the T cells are found in the blood at five years, then the subjects will continue to be seen once a year until the T cells are no longer found in the blood for a maximum of 15 years. If the T cells are no longer found in the blood at 5 years, then the subject will be contacted by the Study Physician for the next 10 years.
|Condition or disease||Intervention/treatment||Phase|
|Carcinoma, Non-Small-Cell Lung||Genetic: Autologous Genetically modified T cells, NY-ESO-1ᶜ²⁵⁹T||Phase 1 Phase 2|
This is a single-arm study of genetically engineered NY-ESO-1ᶜ²⁵⁹T cells in HLA-A*0201, HLA-A*0205 and/or HLA-A*0206 positive subjects with advanced (Stage IIIb or IV) NSCLC. Subjects with measurable disease will be screened for general health, performance status and disease stage. Following screening, subjects meeting all eligibility will undergo a large-volume leukapheresis to obtain cells for the manufacture of autologous NY-ESO-1ᶜ²⁵⁹ TCR bearing T cells. When the NY-ESO-1ᶜ²⁵⁹T cells are available, subjects will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine on Day -7, Day -6 and Day -5 followed by the cell infusion on Day 1.
Subjects will visit the clinic for safety and efficacy assessments daily from T cell infusion (Day 1) through Day 5, Days 8, 10, 12, and then weekly until week 6 and then at 8, 10, 12, 16, 20 and 24 weeks, and every 3 months until 2 years and then every 6 months until progression of their disease (or withdrawal of consent for the interventional portion of the study)
Subjects who have a confirmed response (or have stable disease for >4 months) but subsequent disease progression following the initial infusion and whose tumor continues to express the appropriate antigen target may be eligible for a second infusion.
All subjects, completing or withdrawing from the interventional portion of the study, will enter a 15-year long-term follow-up phase for observation of delayed adverse events. All subjects will continue to be followed for overall survival during the long-term follow-up phase.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Open-Label Clinical Trial Evaluating the Safety and Efficacy of Autologous T Cells Expressing Enhanced TCRs Specific for NY-ESO-1 in Subjects With Stage IIIb or Stage IV Non-Small Cell Lung Cancer (NSCLC)|
|Study Start Date :||November 2015|
|Estimated Primary Completion Date :||January 2019|
|Estimated Study Completion Date :||January 2019|
|Experimental: Autologous Genetically modified T cells, NY-ESO-1ᶜ²⁵⁹T||
Genetic: Autologous Genetically modified T cells, NY-ESO-1ᶜ²⁵⁹T
- Number of subjects with adverse events (AE), including serious adverse events (SAE) [ Time Frame: 24 months ]Determine if treatment with autologous genetically modified T cells, (NY-ESO-1ᶜ²⁵⁹T) is safe and tolerable through assessment of AEs, including SAEs; laboratory assessments, including chemistry, hematology, coagulation and anti-NY-ESO-1ᶜ²⁵⁹T antibodies; cardiac and pulmonary assessments, including ECG and pulmonary function (pulse oximetry) , persistence of NY-ESO-1ᶜ²⁵⁹T, and circulating cytokines.
- Proportion of subjects with a confirmed Complete Response (CR) or Partial Response (PR) [ Time Frame: 24 months ]Evaluation of the efficacy of the treatment by assessment of the Overall Response Rate according to RECIST v1.1
- Interval between the date of first T cell infusion dose and first documented evidence of CR or PR [ Time Frame: 24 months ]Evaluation of the efficacy of the treatment by assessment of time to first response
- Interval between the date of first documented evidence of CR or PR until first documented disease progression or death due to any cause [ Time Frame: 24 months ]Evaluation of the efficacy of the treatment by assessment of duration of response
- Interval between the date of first documented evidence of SD until first documented disease progression or death due to any cause [ Time Frame: 24 months ]Evaluation of the efficacy of the treatment by assessment of duration of stable disease
- Interval between the date of first T cell infusion and the earliest date of disease progression or death due to any cause [ Time Frame: 24 months ]Evaluation of the efficacy of the treatment by assessment of progression-free survival
- Interval between the date of first T cell infusion and date of disease progression or death due to any cause [ Time Frame: 24 months ]Evaluation of the efficacy of the treatment by assessment of overall survival
- Correlation of NY-ESO-1ᶜ²⁵⁹T persistence, phenotype and functionality with response to treatment [ Time Frame: 24 months ]Flow cytometry will be used to assess the phenotype of transduced T cells in the manufactured product and in post-infusion samples.
- Investigation of antigen loss (NY-ESO-1) as an escape mechanism [ Time Frame: 24 months ]Assessment of expression of NY-ESO-1 in tumor samples after T cell infusion
- Correlation of clonal outgrowth of T cell populations with response following T cell infusion [ Time Frame: 24 months ]Assessment of the polyclonality status of the T cell population in peripheral blood (and tumor samples, if available) by TCR sequencing
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): NCT02588612
|United States, California|
|City of Hope|
|Duarte, California, United States, 91010|
|United States, Florida|
|University of Miami, Sylvester Comprehensive Cancer Center|
|Miami, Florida, United States, 33136|
|H. Lee Moffitt Cancer Center|
|Tampa, Florida, United States, 33612|
|United States, Maryland|
|University of Maryland, Greenebaum Cancer Center|
|Baltimore, Maryland, United States, 21157|
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|United States, Missouri|
|Washington University, School of Medicine|
|Saint Louis, Missouri, United States, 63110|
|United States, Tennessee|
|Tennessee Oncology- Sarah Cannon Research Institute|
|Nashville, Tennessee, United States, 37203|
|United States, Texas|
|The University of Texas MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||John Heymach, MD, PhD||M.D. Anderson Cancer Center|