MAGE A10ᶜ⁷⁹⁶T for Advanced NSCLC
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|ClinicalTrials.gov Identifier: NCT02592577|
Recruitment Status : Recruiting
First Posted : October 30, 2015
Last Update Posted : January 11, 2018
This first time in human 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*02:01 and/or HLA-A*02:06 and a tumor test positive for MAGE A10 protein 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. The study will evaluate three different cell dose levels in order to find out the target cell dose. Once the target cell dose is determined, additional subjects will be enrolled to further test the safety and effects at this cell dose.
Subjects will be seen frequently by the Study Physician right after receiving their T cells back and up to first 6 months. After that, subjects will be seen every three months. If subjects have disease progression or withdraw from the study, they will then be entered into a long-term follow up for safety monitoring. 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|
|Non-Small Cell Lung Cancer Carcinoma||Biological: Autologous Genetically modified T cells, MAGEA10ᶜ⁷⁹⁶T||Phase 1|
This first time in human study is a single-arm study of genetically engineered MAGE A10ᶜ⁷⁹⁶T cells in HLA-A*02:01 and/or HLA-A*02:06 positive subjects with advanced (Stage IIIb or IV) NSCLC. Subjects 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 MAGE A10ᶜ⁷⁹⁶TCR bearing T cells. When the MAGE A10ᶜ⁷⁹⁶T cells are available, subjects will receive lymphodepleting chemotherapy with cyclophosphamide on Days -7 and -6 or cyclophosphamide and fludarabine on Days -7, Day -6, and Day -5 followed by the T cell infusion on Day 1.
This trial is a dose escalation trial that will evaluate 3 doses of transduced cells administered after a lymphodepleting chemotherapy regimen using a 3+3 dose escalation design. The doses for each cell dose group are as follows.
Group 1a and 1b: 0.1 x 10⁹ (range: 0.08 x 10⁹-0.12 x 10⁹) transduced cells. Group 2: 1 x 10⁹ (range: 0.8 x 10⁹- 1.2 x 10⁹) transduced cells. Group 3: 5 x 10⁹ (range: 1 x 10⁹- 6 x 10⁹) transduced cells.
There will be a 21-day staggering of treatment in between the first 3 subjects treated in the study. For subsequent subjects a 7-day stagger between treatments will be followed.
NOTE: If a DLT occurs in Group 1 or Group 2 which requires expansion of the group (n=6), then a 14-day stagger would be implemented in Group 2 or 3, respectively. The study will enroll 12-24 subjects to evaluate DLTs and determine target dose. The sample size of the target cell dose may be expanded up to 10 subjects to characterize safety and any preliminary evidence of antitumor activity. The Safety Review Committee (SRC) may recommend adding additional patients to a given group (not to exceed 9 subjects in total in any group apart from target dose expansion group) resulting in a potential maximum number of 37 subjects treated.
Subjects will visit the clinic for safety 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 Phase 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 :||28 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Dose Escalation Open Label Clinical Trial Evaluating the Safety and Efficacy of MAGE A10ᶜ⁷⁹⁶T in Subjects With Stage IIIb or Stage IV Non-Small Cell Lung Cancer (NSCLC)|
|Study Start Date :||November 2015|
|Estimated Primary Completion Date :||April 2019|
|Estimated Study Completion Date :||April 2019|
|Experimental: Autologous Genetically modified T cells, MAGEA10ᶜ⁷⁹⁶T||Biological: Autologous Genetically modified T cells, MAGEA10ᶜ⁷⁹⁶T|
- Number of subjects with dose-limiting toxicity (DLT) and adverse events (AE), including serious adverse events (SAE) [ Time Frame: 24 months ]Determine if treatment with autologous genetically modified T cells, (MAGE A10ᶜ⁷⁹⁶T ) is safe and tolerable through assessment of DLTs, AEs, including SAEs; laboratory assessments, including chemistry, hematology, and coagulation and anti-MAGE A10ᶜ⁷⁹⁶T antibodies; cardiac and pulmonary assessments, including ECG and pulmonary function (pulse oximetry), persistence of MAGE A10ᶜ⁷⁹⁶T, 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 MAGE A10ᶜ⁷⁹⁶T 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 (MAGE A10) as an escape mechanism [ Time Frame: 24 months ]Assessment of expression of MAGE A10 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): NCT02592577
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02592577
|Contact: Ben Creelan, MD, MS||813-745-3050|
|Contact: Ani Suwarno|
|United States, California|
|City of Hope||Recruiting|
|Duarte, California, United States, 91010|
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|Stanford Cancer Center||Recruiting|
|Palo Alto, California, United States, 94304|
|Contact: Jordan S Preiss, BA 650-723-1002 firstname.lastname@example.org|
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|University of Miami Sylvester Comprehensive Cancer Center||Recruiting|
|Miami, Florida, United States, 33136|
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|H. Lee Moffitt Cancer Center||Recruiting|
|Tampa, Florida, United States, 33612|
|Contact: Jeff L Edelman, MS 813-745-1040 Jeffrey.Edelman@moffitt.org|
|Contact: Ani Suwarno 813-745-6779 Ani.Suwarno@moffitt.org|
|Principal Investigator: Ben Creelan, MD, MS|
|United States, Georgia|
|Winship Cancer Institute of Emory University||Recruiting|
|Atlanta, Georgia, United States, 30322|
|Contact: Shantina N Walls, BS 404-778-4995 firstname.lastname@example.org|
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|United States, Maryland|
|University of Maryland, Greenebaum Cancer Center||Recruiting|
|Baltimore, Maryland, United States, 21157|
|Contact: Brett Goldberger, MS 410-328-1160 email@example.com|
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|United States, Massachusetts|
|Massachusetts General Hospital||Recruiting|
|Boston, Massachusetts, United States, 02114|
|Contact: Justin F Gainor, M.D. 617-724-4000 firstname.lastname@example.org|
|Principal Investigator: Justin F Gainor, M.D.|
|United States, Missouri|
|Washington University, School of Medicine||Recruiting|
|Saint Louis, Missouri, United States, 63110|
|Contact: Melissa Meredith 314-362-4140 email@example.com|
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|United States, Ohio|
|Ohio State University Wexner Medical Center||Recruiting|
|Columbus, Ohio, United States, 43210|
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|United States, Tennessee|
|Tennessee Oncology- Sarah Cannon Research Institute||Recruiting|
|Nashville, Tennessee, United States, 37203|
|Contact 615-329-7400 email@example.com|
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|United States, Texas|
|The University of Texas MD Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Matthew Parker, RN 713-745-6767 firstname.lastname@example.org|
|Contact: Sylvia Y Contreras|
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|Princess Margaret Cancer Centre||Recruiting|
|Toronto, Ontario, Canada, M5G1X6|
|Contact: Penelope Bradbury, MD 416-946-4501 ext 3544 TIP@uhn.ca|
|Principal Investigator: Penelope Bradbury, MD|
|University College Hospital Macmillan Cancer Centre||Recruiting|
|London, United Kingdom, WC1E 6AG|
|Contact: Gemma Hector 07852219920 Gemma.Hector@uclh.nhs.uk|
|Contact: Krishna Patel email@example.com|
|Principal Investigator: Martin D Forster, MBBS, FRCP, PhD|
|Study Chair:||Ben Creelan, MD, MS||H. Lee Moffitt Cancer Center|