MAGE-A10ᶜ⁷⁹⁶T for Urothelial Cancer, Melanoma or Head and Neck Cancers
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|ClinicalTrials.gov Identifier: NCT02989064|
Recruitment Status : Recruiting
First Posted : December 12, 2016
Last Update Posted : January 11, 2018
|Condition or disease||Intervention/treatment||Phase|
|Urinary Bladder Cancer Head and Neck Cancer Melanoma||Genetic: Autologous genetically modified MAGE A10ᶜ⁷⁹⁶T cells||Phase 1|
This Phase 1 study is designed as a cell dose escalation trial in HLA-A2*02:01 and -A*02:06 subjects with MAGE-A10 positive urothelial, melanoma or head and neck tumors. 16-22 subjects with inoperable or metastatic (advanced) urothelial cancer, head and neck cancer, or melanoma will be treated in this study. The study will enroll subjects using a modified 3+3 cell dose escalation design to evaluate dose limiting toxicities and determine the target cell dose range. Following the dose escalation phase additional subjects will be enrolled until 10 subjects are treated at the target cell dose range to further characterize safety, tolerability and anti-tumor activity.
Subjects may be screened in the Screening Protocol (ADP-0000-001) for the presence of HLA-A2*02:01 and/or HLA-A*02:06 and have MAGE-A10 expression in the tumor. The absence of HLA-A*02:05 in either allele, HLA-B*15:01 or HLA-B*46:01 will also be assessed. The presence of HLA A*02 null allele (designated with an "N", e.g. A*02:32N) as the sole HLA-A*02 allele will also be assessed as these are study exclusion criteria.
Leukapheresis is performed to obtain cells for the manufacture of autologous MAGE-A10ᶜ⁷⁹⁶T cell receptor (TCR) bearing T cells. Leukapheresis should be performed as soon as possible after the subject is determined to be eligible for study participation.
When the manufactured MAGE-A10ᶜ⁷⁹⁶T cells are available, subjects will undergo lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by infusion of MAGE-A10ᶜ⁷⁹⁶T on Day 1.
Safety and tolerability as well as anti-tumor activity and biomarker assessments to be conducted at each visit are outlined in the Schedule of Procedures. Anti-tumor activity will be assessed using RECIST v1.1 criteria.
All subjects, completing or withdrawing from the interventional portion of the study, will be rolled over to a long term follow-up (LTFU) protocol for observation of delayed adverse events for 15 years post-infusion in accordance with FDA and EMA requirements for gene therapy clinical trials as well as for overall survival. FDA and EMA follow-up requirements for gene therapy clinical trials, continues after the subject has been confirmed to have progression of disease.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||22 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase 1 Cell Dose Escalation Study to Assess the Safety and Tolerability of Genetically Engineered MAGE-A10ᶜ⁷⁹⁶T in HLA-A2+ Subjects With MAGE-A10 Positive Urothelial, Melanoma or Head and Neck Tumors|
|Study Start Date :||October 2016|
|Estimated Primary Completion Date :||November 2019|
|Estimated Study Completion Date :||May 2020|
|Experimental: Autologous genetically modified MAGE A10ᶜ⁷⁹⁶T cells||Genetic: Autologous genetically modified MAGE A10ᶜ⁷⁹⁶T cells|
- Number of subjects with adverse events (AE), including serious adverse events (SAE). [ Time Frame: 3 years ]Determine if treatment with autologous genetically modified T cells, (MAGE A10ᶜ⁷⁹⁶T ) is safe and tolerable through laboratory assessments including chemistry, hematology, coagulation and anti-MAGE-A10 antibodies; and cardiac assessments, including ECG/troponin.
- Evaluation of the persistence of genetically modified T cells [ Time Frame: 3 years ]Evaluation of the persistence of the infused T cells in the periphery.
- Measurement of RCL in genetically modified T cells. [ Time Frame: 3 years ]Evaluation of RCL in Subject PBMCs using PCR-based assay.
- Proportion of subjects with a confirmed Complete Response (CR) and/or Partial Response (PR). [ Time Frame: 3 years ]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: 3 years ]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: 3 years ]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: 3 years ]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: 3 years ]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 death due to any cause. [ Time Frame: 3 years ]Evaluation of the efficacy of the treatment by assessment of overall survival.
- Mean fluorescence intensity (expression) of specific surface markers on gene-modified T cells. [ Time Frame: 3 years ]Killing profile and cytokine profile of genetically modified T cells will be evaluated using flow cytometry.
- Evaluation of MAGE A10 expression pre and post infusion using IHC. [ Time Frame: 3 years ]Determine MAGE A10 expression post therapy.
- Measure polymorphisms in cytokine genes. [ Time Frame: 3 years ]Association of polymorphisms with cytokine production.
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): NCT02989064
|Contact: David Hong, MD||713-563-1930|
|United States, Massachusetts|
|Massachusetts General Hospital||Recruiting|
|Boston, Massachusetts, United States, 02114|
|Contact: Ryan Sullivan, MD 617-724-4000 email@example.com|
|Principal Investigator: Ryan Sullivan, MD|
|United States, Tennessee|
|Tennessee Oncology - Sarah Cannon Research Institute||Recruiting|
|Nashville, Tennessee, United States, 37203|
|Contact 615-339-4214 firstname.lastname@example.org|
|Principal Investigator: Melissa Johnson, MD|
|United States, Texas|
|MD Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Danxia Ke 713-792-4384 email@example.com|
|Contact: Ly M Nguyen|
|Principal Investigator: David S Hong, MD|
|Princess Margaret Cancer Centre||Recruiting|
|Toronto, Ontario, Canada, M5G1X6|
|Contact: Marcus Butler, MD 416-946-4501 TIP@uhn.ca|
|Contact: Anna Spreafico|
|Principal Investigator: Marcus Butler, MD|
|Principal Investigator:||David Hong, MD||M.D. Anderson Cancer Center|