Valutazione del follow-up per eventi avversi ritardati correlati alla terapia genica dopo la partecipazione a studi clinici nel settore dell'oncologia pediatrica

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 up to 15-year follow-up of participants, this study will remain open until 2050.