Long-term Follow-up of Subjects Treated With CARv3-TEAM-E T Cells

Study Overview
=================
Brief Summary
-----------------
This is a single site, non-randomized, open-label, long-term safety and efficacy follow-up Phase 1 study for subjects who have been treated with CARv3-TEAM-E T cells in clinical Study DF/HCC IRB #20-532 (the main study), that evaluated the safety and efficacy of CARv3-TEAM-E T cells in subjects with newly diagnosed or recurrent glioblastoma

Detailed Description
-----------------
This is a single site, non-randomized, open-label, long-term safety and efficacy follow-up Phase 1 study for subjects who have been treated with CARv3-TEAM-E T cells in clinical Study DF/HCC IRB #20-532 (the main study), that evaluated the safety and efficacy of CARv3-TEAM-E T cells in subjects with newly diagnosed or recurrent glioblastoma. CARv3-TEAM-E drug product is defined as autologous T lymphocytes transduced with a CAR lentiviral vector encoding a chimeric antigen receptor targeting human EGFRvIII antigen and a T cell engaging antibody molecule (TEAM) targeting wildtype EGFR. CARv3-TEAM-E T cells are administered in subjects up to six times in main Study #20-532. No investigational treatment will be administered in this study. The United States Food and Drug Administration (FDA, 2018) recommend long-term follow-up for subjects treated with gene therapy drug products to monitor for selected adverse events (AEs) and the durability of clinical response. After the subjects in the parent study has been completed (24 months after CARv3-TEAM-E T cells infusion, or <24 months after CARv3-TEAM-E infusion if subject discontinues due to disease progression or any other reason), subjects will be asked to participate in a long-term follow-up study.

Official Title
-----------------
Long-term Follow-up of Subjects Treated With CARv3-TEAM-E T Cells

Conditions
-----------------
Glioblastoma Recurrent, EGFR vIII Mutant, Newly Diagnosed Glioblastoma, EGFRvIII Mutant, Recurrent Glioblastoma, EGFR vIII Negative

Intervention / Treatment
-----------------
* Diagnostic Test: Disease assessments
* Procedure: Tumor Biopsy
* Diagnostic Test: Blood test


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: - Subjects will be asked to participate leading up to the last Study #20-532 visit. Subjects meeting the following criteria are eligible for study participation: Provision of voluntary written informed consent by subject CARv3-TEAM-E T cells were administered in DF/HCC IRB Study #20-532 Able to comply with study requirements Exclusion Criteria: Subjects meeting the following criteria are to be excluded from study participation: Subject has disease progression AND has 2 consecutive VCN measurements at least 1 month apart, at least 6 months after drug product infusion where testing demonstrates undetectable VCN (<0.0003 vector copies per diploid genome) in peripheral blood cells. Withdrew consent to Study #20-532.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CARv3-TEAM-E T cells<br>Eligibility to participate on this study if enrolled on study 20-532 and received infusion of CARv3-TEAM-E T The research study procedures include evaluations and follow up visits: Timepoints of each evaluation and follow up visit- per protocol Medical History/Physical Exam Blood Test Assessment of Disease: CT (Computerized Tomography) scan or PET-CT (Positron Emission Tomography-Computerized Tomography) scans. Tumor biopsy. Data Collection Biobanking | Diagnostic Test: Disease assessments<br>* CT (Computerized Tomography) scan or PET-CT (Positron Emission Tomography-Computerized Tomography) scans as per protocol<br>Procedure: Tumor Biopsy<br>* Tumor Biopsy per protocol<br>Diagnostic Test: Blood test<br>* Blood Test per protocol<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive | 1 month | 
| Overall Survival | defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive | 6 months | 
| Overall Survival | defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive | 12 months | 
| Overall Survival | defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive | 24 months | 
| Progresison Free Survival | PFS is defined as the number of days from the day of CARv3-TEAM-E T cells treatment to the first documented disease progression or date of death, whichever occurs first. Patients who are lost to follow up without a known date of progression or death due to any cause will be censored in the analysis at the date of their last available tumor assessment. | 1 month | 
| Progresison Free Survival | PFS is defined as the number of days from the day of CARv3-TEAM-E T cells treatment to the first documented disease progression or date of death, whichever occurs first. Patients who are lost to follow up without a known date of progression or death due to any cause will be censored in the analysis at the date of their last available tumor assessment. | 6 months | 
| Progresison Free Survival | PFS is defined as the number of days from the day of CARv3-TEAM-E T cells treatment to the first documented disease progression or date of death, whichever occurs first. Patients who are lost to follow up without a known date of progression or death due to any cause will be censored in the analysis at the date of their last available tumor assessment. | 12 months | 
| Progresison Free Survival | PFS is defined as the number of days from the day of CARv3-TEAM-E T cells treatment to the first documented disease progression or date of death, whichever occurs first. Patients who are lost to follow up without a known date of progression or death due to any cause will be censored in the analysis at the date of their last available tumor assessment. | 24 months | 
| New incidence or exacerbation of a pre-existing neurologic disorder or prior rheumatologic or other autoimmune disorder | An annual physical exam will be conducted for surveillance of manifestations indicative of oncoretroviral diseases. | Up to 15 Years | 
| New incidence of a hematologic disorder | An annual physical exam will be conducted for surveillance of manifestations indicative of oncoretroviral diseases. | up to 15 years | 
| Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v 5.0 | ersion 5.0 of the NCI Common Terminology Criteria for Adverse Events (CTCAE) | base line up to 15 years | 
| Vector-derived RCL | Archiving of samples for potential detection of vector-derived RCL. RCL testing will be monitored at the central RCL lab (Indiana University) by a suitable qPCR assay for detection of the lentiviral vector (VSV-g DNA). | baseline and in 3 months, 6 months, and annually up to 15 years | 
| Assessment of CAR T cells persistence by VCN in peripheral blood | VCN will be performed in DNA from whole blood to monitor for persistence of vector sequence | baseline and in 3 months, 6 months, every 6 months up to 5 years, and annually up to 15 years | 
| Disease specific response | Response Assessment in Neuro-Oncology Criteria (RANO) | Every 6 Months through 5 years, | 
| Disease specific response | Response Assessment in Neuro-Oncology Criteria (RANO) | At year 7, year 10 and up through 15 Years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Glioblastoma Recurrent, EGFR vIII mutant, Newly Diagnosed Glioblastoma, EGFR vIII mutant, Recurrent Glioblastoma, EGFR vIII negative, CARv3-TEAM-E T cells