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

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

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.

Study Overview

• Status: Terminated
• Conditions: Solid and Hematological Malignancies
• Intervention / Treatment: Genetic: Genetically engineered T Cell Receptors

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G1X6
      • Princess Margaret Cancer Centr
• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects with solid or hematological malignancies rolling over from interventional study where they were treated with a genetically modified T-cell receptor

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Genetically engineered T Cell Receptor- treated; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Adaptimmune
• Investigators: Principal Investigator: Marcus Butler, MD, Princess Margaret Cancer Centr

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2018
• Primary Completion (Actual): July 24, 2018
• Study Completion (Actual): July 24, 2018

Study Registration Dates

• First Submitted: January 2, 2018
• First Submitted That Met QC Criteria: January 2, 2018
• First Posted (Actual): January 5, 2018

Study Record Updates

• Last Update Posted (Actual): January 7, 2021
• Last Update Submitted That Met QC Criteria: January 5, 2021
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Cell Therapy; Metastatic; Immuno-oncology; T Cell Therapy; T Cell Receptor; SPEAR T Cell; Long Term Follow Up; Genetically Engineered
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Hematologic Diseases; Hematologic Neoplasms
• Other Study ID Numbers: ADP-0000-003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No