Adult, CAR-T, Disease-Free Survival, Duty to Follow Up, Long Term Adverse Effects, Overall Survival, Progression-Free Survival
Conditions
Keywords
Long-Term Follow-up to CAR-T Cells, Follow-up Studies
Brief summary
This is a single site, non-randomized, open-label, long-term safety and efficacy follow-up study for Phase 1 studies that evaluate the safety and efficacy of CAR T cells: NCT05660369 (DF/HCC# 22-175) and NCT06026319 (DF/HCC# 23-474).
Detailed description
This is a long-term safety and efficacy follow-up study for subjects who have been treated with CAR T cells in corresponding Phase I main studies that evaluated the safety and efficacy of CAR T cells in subjects. No investigational treatment will be administered in this study. The FDA (2020) recommends long-term follow up for subjects treated with gene therapy drug products to monitor for delayed adverse events (AEs), as well as durability of clinical response. Therefore, after monitoring of subjects in the main studies has been completed (24 months after CAR T cells infusion, or \<24 months after CAR T cells infusion if subject terminated early due to disease progression or due to discontinuing corresponding main study for any reason), subjects will be asked to participate in a long-term follow-up study (LTFU). Subjects will be followed for up to 15 years following their last CAR T cells infusion in the corresponding main study.
Interventions
DIAGNOSTIC_TESTDisease assessments
CT (Computerized Tomography) scan or PET-CT (Positron Emission Tomography-Computerized Tomography) scans as per protocol
PROCEDURETumor Biopsy
Tumor Biopsy per protocol
DIAGNOSTIC_TESTBlood test
Blood Test per protocol
Sponsors
Marcela V. Maus, M.D.,Ph.D.
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subjects will be asked to participate leading up to the last DF/HCC corresponding main study visit. Subjects meeting the following criteria are eligible for study participation: * Provision of voluntary written informed consent by subject * CAR T cells were administered in DF/HCC IRB corresponding main study
Exclusion criteria
Subjects meeting the following criterion are to be excluded from study participation: \- Subject unable to comply with study requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 1 month | defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive |
| Progresison Free Survival | 1 month | 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. |
Countries
United States
Contacts
CONTACTMatthew J Frigault, MD
PRINCIPAL_INVESTIGATORMatthew J Frigault, MD
Massachusetts General Hospital
Outcome results
None listed