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

Not yet recruiting

• Conditions: Long Term Adverse Effects; CAR-T; Duty to Follow Up; Adult; Progression-Free Survival; Disease-Free Survival; Overall Survival
• Interventions: Diagnostic Test: Disease assessments; Procedure: Tumor Biopsy; Diagnostic Test: Blood test

• Registration Number: NCT05024175
• Lead Sponsor: Massachusetts General Hospital

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.

Study Timeline

• Status Verified: 2021-08
• Study First Submitted: 2021-08-23
• Study First Submitted QC: 2021-08-23
• Last Update Submitted: 2021-08-23
• Study First Posted: 2021-08-27
• Last Update Posted: 2021-08-27
• Study Start: 2021-12
• Primary Completion: 2038-08-01
• Study Completion: 2039-08-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 18

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
CAR T cells	Disease assessments	* Eligibility to participate on this study if enrolled on a DF/HCC IRB corresponding main study and received infusion of CAR T cells * 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
CAR T cells	Tumor Biopsy	* Eligibility to participate on this study if enrolled on a DF/HCC IRB corresponding main study and received infusion of CAR T cells * 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
CAR T cells	Blood test	* Eligibility to participate on this study if enrolled on a DF/HCC IRB corresponding main study and received infusion of CAR T cells * 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

Primary Outcome Measures

Name	Time	Method
Overall Survival	From post-CAR T cells infusion date until documented date of death from any cause, assessed post treatment every 6 months through 5 years and then annually up to 15 years	The time from post-CAR T cells infusion to the date of death.
Progresison Free Survival	24 months	PFS is defined as the number of days from the day of CAR 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.
New incidence or exacerbation of a pre-existing neurologic disorder or prior rheumatologic or other autoimmune disorder	Up to 15 Years	An annual physical exam will be conducted for surveillance of manifestations indicative of oncoretroviral diseases.
New incidence of a hematologic disorder	up to 15 years	An annual physical exam will be conducted for surveillance of manifestations indicative of oncoretroviral diseases.
Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v 5.0	up to 15 years	NCI Common Terminology Criteria for Adverse Events (CTCAE)
Vector-derived RCL	baseline and in 3 months, 6 months, and annually up to 15 years	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).
Assessment of CAR T cells persistence by VCN in peripheral blood	baseline and in 3 months, 6 months, every 6 months up to 5 years, and annually up to 15 years	VCN will be performed in DNA from whole blood to monitor for persistence of vector sequence
Progression-free Survival	From post-CAR T cells infusion date until date of first documented disease progression or date of death from any cause, assessed up to 15 years post treatment	The number of days from the day of CAR 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.

Trial Locations

Locations (1)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States