Hi @cmdickens
Let’s see if any of our developers recognize the issue. Maybe there was a small change in the later releases. I’ve cross-posted over to our Admin Matrix channel but let’s keep the conversation here.
If you would like to post back the galaxy.log content from right before, during, and after that would be helpful (redact anything private and try to keep the format intact by quoting, or just post text with line breaks and we will reformat). 
If there is anything special about your server, you can include those details too.
For example, more details your proxy configuration would be helpful. Your database choice may matter too. I’m not sure if you mean the FTP directory is on the webserver’s head node, or the same node as the database, or just another cluster node in your local job execution environment (as opposed to a remote cluster?).
Then, was your server restarted during this time frame? Or is this error showing up spontaneously, but only for larger files, not smaller ones. And, only when both large and small are using the FTP directory transfer (during restart or not?) or do you mean regular file Upload (browsing, URL) works Ok. I’m just trying to pinpoint the series of events and observations for the troubleshooting.
Let’s start there, thanks!
XRef → Private Galaxy Servers