Long Term Follow up of Subjects Exposed to Genetically Engineered T Cell Receptors

Study Overview
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Brief Summary
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Subjects who previously took part in an Adaptimmune study and received genetically changed T cells (including but not limited to MAGE-A10ᶜ⁷⁹⁶T and MAGE-A4ᶜ¹º³²T) are asked to take part in this long term follow-up study. Subjects will be asked to join this study once they complete the parent interventional study. The purpose of this study is to find out if the genetically changed T cells that subjects received in the parent study have any long-term side effects. No additional study drug will be given, but subjects can receive other therapies for their cancer while they are being followed for long term safety in this study. For a period of 15 years starting from last administration of the genetically changed T cells, subjects will visit their study doctor for a check-up and to have blood tests to look for any changes that might have happened because of the genetically changed T cells.

Detailed Description
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This is a non-therapeutic, multi-center, long-term follow-up (LTFU) study of subjects who have received lentivirus-mediated genetically engineered T Cell Receptors in an Adaptimmune sponsored clinical trial. The study is designed in accordance with FDA and EMA guidance on gene therapy trials. The study involves up to 15 years post-infusion monitoring of subjects who have been exposed to lentivirus-mediated gene transfer in Adaptimmune clinical studies. The study will include subjects who have received various T cell receptors including but not limited to MAGE-A10ᶜ⁷⁹⁶T and MAGE-A4ᶜ¹º³²T. Subjects will undergo clinical evaluation (i.e., new medical history, physical exam, adverse events, and exposure to mutagenic agents, anti-cancer therapies and investigational products in other clinical studies) with careful attention to adverse events possibly related to gene transfer or lentivirus-induced diseases. Blood samples will be collected for evaluating persistence of cells with lentiviral vector sequences, the detection of replication competent lentivirus (RCL), and chemistry and hematology laboratory assessments. Subjects will be followed for survival.

Official Title
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Long Term Follow-up of Subjects Exposed to Genetically Engineered Tumor Antigen Specific T Cell Receptors

Conditions
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Solid and Hematological Malignancies

Intervention / Treatment
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* Genetic: Genetically engineered T Cell Receptors


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have received T cell receptor therapy in an Adaptimmune clinical study Subjects who have provided informed consent prior to their study participation Exclusion Criteria: Not applicable

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Genetically engineered T Cell Receptor- treated<br>Long term follow-up of subjects with solid or hematological malignancies who have received lentivirus-mediated genetically engineered T Cell Receptors in a previous trial | Genetic: Genetically engineered T Cell Receptors<br>* No study drug is administered in this study. Subjects who received lentivirus-mediated genetically engineered T Cell Receptors in a previous trial will be evaluated in this trial for long-term safety and efficacy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with specific Long Term Follow-Up adverse events (AEs), including serious adverse events (SAEs) associated with administration of autologous T cell receptors that have been genetically modified by lentiviral vectors. | New malignancies New incidence or exacerbation of a pre-existing neurologic disorder New incidence or exacerbation of a prior rheumatologic or other autoimmune disorder New incidence of a hematologic disorder Opportunistic and/or serious infections Unanticipated illness and/or hospitalization deemed related to gene modified cell therapy | 15 years post last treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of Replication Competent Lentivirus (RCL) in genetically modified T cells | Subjects' peripheral blood samples will be used to evaluate RCL | 15 years post last treatment | 
| Persistence of genetically modified cells in the body | Peripheral blood samples will be used to evaluate persistence | 15 years post last treatment | 
| Assess the pattern of vector integration sites if at least 1% of cells in the surrogate sample are positive for vector sequences by PCR | Number of samples positive for vector integration by PCR | 15 years post last treatment | 
| Overall Survival (OS) post-infusion | OS defined as the interval between the date of first T cell infusion and date of death due to any cause | 15 years post last treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cell Therapy, T Cell Therapy, SPEAR T Cell, Immuno-oncology, Metastatic, T Cell Receptor, Long Term Follow Up, Genetically Engineered