Follow-Up Evaluation for Gene-Therapy-Related Delayed Adverse Events After Participation in Pediatric Oncology Branch Clinical Trials

Follow-Up Evaluation for Gene-Therapy Related Delayed Adverse Events After Participation in Pediatric Oncology Branch Clinical Trials

Background:

- Gene therapy involves changing the genes inside the body s cells to stop disease. It is very closely regulated. People who have had this therapy may have problems months or even years later. Researchers do not know the long-term side effects, so they want to study people who have had the therapy. They want the study to continue over the next 15 years.

Objective:

- To study over time the negative side effects from genetically engineered cellular therapy. This will be studied in people who have been in Pediatric Oncology Branch (POB) gene therapy trials.

Eligibility:

- People who are currently or were previously in a research study with gene therapy in the National Cancer Institute POB.

Design:

• Participants blood will be tested right before they get the genetically changed cells. They will get the cells as part of another study.
• For the next year, they will come back to the clinic or see their doctor at home at least every 3 months. They will answer questions about their health and blood will be drawn.
• For the next 5 years, they will go to the clinic or see their own doctor once a year. They will have physical exam and blood will be drawn.
• For 10 years after that, they will be asked every year for health information.
• Participants will keep their contact information up to date with researchers. They may be phoned for more health information.
• If the participant was under 18 years old when given the gene therapy and turns 18 during this follow-up, they will be asked to sign a new consent form when they turn 18.

Study Overview

• Status: Enrolling by invitation
• Conditions: Solid Tumors; Hematologic Malignancies; Pediatric Cancers
• Intervention / Treatment: Drug: anti-CD19 CAR

Detailed Description

Background:

• Study subjects exposed to gene therapy interventions may be at risk for delayed or longterm adverse consequences. The U.S. Food and Drug Administration (FDA) has issued Long Term Follow-up After Administration of Human Gene Therapy Products: Guidance for Industry and Testing of Retroviral Vector-Based Human Gene Therapy Products for Replication Competent Retrovirus During Product Manufacture and Patient Follow-up: Guidance for Industry, which outlines a framework to assess the risk of gene therapy-related delayed adverse events and the essential elements appropriate for the conduct of long-term follow up observations.
• Accordingly, some vector designs (i.e. use of an adenovirus), based on duration of persistence accompanied by cumulative preclinical and clinical evidence, may require shorter periods of observation than other vector designs (i.e. use of a lentivirus).

Objective:

-To conduct long term safety evaluations for adverse events associated with genetically engineered cellular therapy in subjects who have participated in Pediatric Oncology Branch (POB) clinical trials.

Eligibility:

-Subjects who are planned to receive or have received at least one dose of a genetically engineered cellular therapy on a POB gene therapy clinical trial are eligible to participate.

Design:

• Subjects will be evaluated for long term safety and occurrence of adverse events according to the requirements established by the FDA guidance and the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines), to include:

• Long term follow-up after genetically engineered cellular therapy may include:

  • Post-cell infusion evaluations for T-Cell persistence (if applicable)
  • Monitoring for replication-competent retrovirus (RCR) or replication-competent lentivirus (RCL)
  • Physical examination
  • Questionnaire to detect delayed adverse events
  • Medical record review related to long term adverse events
• To ensure adequate follow up for participants in POB receiving genetically engineered cellular therapy, a maximum accrual of 500 participants will be allowed on this study. To accommodate 15-year follow-up of all participants, this study will remain open until

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 99 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants screening for, participating in, or have participated in a POB gene therapy clinical trial and have received/or be scheduled to receive a genetically engineered cellular therapy.

Description

• INCLUSION CRITERIA:
• Subjects must be identified eligible for, participating in, or have participated in a POB genetically engineered cellular therapy clinical trial and have received/or be scheduled to receive a genetically engineered cellular therapy.
• All monitoring and testing described in this protocol will pertain ONLY to genetically engineered cellular therapy received at the National Institutes of Health (NIH). RCR/RCL monitoring and persistence will NOT be followed for cells administered at another institution.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
1; Patients screening for, participating in, or have participated in a POB gene therapy clinical trial and have received/or be scheduled to receive a genetically engineered cellular therapy.	Drug: anti-CD19 CAR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Conduct long term safety evaluations after gene therapy	PCR results (for RCR/RCL, gene transduced cells)	Every 3 months X 1 year then annually X 15 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Nirali N Shah, M.D., National Cancer Institute (NCI)

Publications and helpful links

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): December 23, 2014
• Primary Completion (Estimated): April 1, 2035
• Study Completion (Estimated): August 1, 2050

Study Registration Dates

• First Submitted: December 11, 2014
• First Submitted That Met QC Criteria: December 11, 2014
• First Posted (Estimated): December 12, 2014

Study Record Updates

• Last Update Posted (Estimated): May 9, 2024
• Last Update Submitted That Met QC Criteria: May 8, 2024
• Last Verified: May 7, 2024

More Information

Terms related to this study

• Keywords: Natural History; T Cell Persistence; Replication Competent Retrovirus (RCR); Replication Competent Lentivirus (RCL)
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Hematologic Diseases; Hematologic Neoplasms
• Other Study ID Numbers: 150028; 15-C-0028

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: .All IPD recorded in the medical record will be shared with intramural investigators upon request.
• IPD Sharing Time Frame: Clinical data available during the study and indefinitely.
• IPD Sharing Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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