LONG-TERM FOLLOW-UP PROTOCOL FOR SUBJECTS TREATED WITH GENE-MODIFIED T CELLS

This is a study for the long-term follow-up (LTFU) of safety and efficacy for
all pediatric and adult subjects exposed to GM T cell therapy in
Celgene-sponsored, or Celgene alliance partner sponsored trials in accordance
with Health Authorities* guidance for subjects treated with gene therapy
products. The treatment trial is also referred to as the parent protocol. No
investigational product will be administered in this LTFU study.

Production of GM T-cells such as CAR require autologous T cells to be
genetically modified by ex vivo transduction using a recombinant viral vector
containing the CAR ribonucleic acid sequence.

In the parent treatment protocols, subjects are treated with GM T-cell products
that use or replication-incompetent, self-inactivating lentiviral vectors
derived from retroviruses. There is a theoretical risk, through a rare
recombination event for example, for the emergence of RCL. Late potential
toxicities may arise from the presence of RCL, unexpected late autonomous
proliferation of infused GM T cells, or insertional mutagenesis/oncogenesis by
integration of the retroviral vector into gene or controlled elements in the
host genome.

Subjects who received at least one infusion of GM T-cells in previous
Celgene-sponsored or Celgene alliance partner sponsored studies will be asked
to participate in this LTFU protocol, upon either premature discontinuation
from, or completion of the parent treatment protocol.

This study has been transitioned to CTIS with ID 2023-504201-36-00 check the CTIS register for the current data.

Per Health Authority guidelines for gene therapy medicinal products that
utilize integrating vectors (eg, lentiviral vectors), long-term safety and
efficacy follow up of treated subjects is recommended.
The primary objectives of this study are as follows:
• To assess the risk of delayed adverse events following exposure to GM T-cells
• To monitor for long-term persistence of GM T cells, including analysis of
vector integration sites, as appropriate.
• To monitor for generation of replication competent lentiviruses (RCL)
• To assess long-term efficacy following treatment with GM T-cells
• Describe growth, and sexual maturity status for subjects who were aged < 18
years at time of GM-T cell therapy

Subjects will be followed for up to 15 years from time of the last GM T cell
infusion.
Pediatric subjects will be monitored for growth and development; this follow-up
may exceed 15 years if Tanner Stage 5 is not achieved at the end of the 15-year
follow-up period.
The End of Study (EOS) visit for each subject, is defined as the date of the
subject*s last visit, which corresponds to the subject*s last planned
evaluation, withdrawal of consent, lost to follow up, or death, whichever
occurs first.
The End of Trial (EOT) is defined as either the date of the last visit of the
last subject or the date of receipt of the last data point from the last
subject that is required for primary analysis, as prespecified in the protocol,
whichever is the later date.

The study procedures may cause complications or discomforts as described in the
subject information sheet.
The EMA and FDA recommends monitoring and follow-up after gene therapy
treatment, to gain information on long-term safety and efficacy after treatment
with genetically modified cells . This LTFU protocol is being conducted to
monitor for long-term safety and efficacy per recommendations. Pediatric
subjects will also be monitored for growth and development within this LTFU
study to assess reproduction and developmental outcomes for this population.
In addition this study will also allow for LTFU for collection of disease
status in subjects who did not experience disease progression on the prior
parent treatment protocol.