I used the FX8 with 4cm with my HK Tubemeister 36 in a couple of clubs and never a ground loop. It just worked. So, there's something being added to your rig that's causing the loop.
I think a lot of it is determined by the amp.
My other rig is a Digitech GSP1101. It's an incredible piece of equipment with the MustBeBeta software, not so great without it.
I use the GSP with a Rivera S120 stereo tube combo from 1990. That amp has hated every pedal and processor that I have thrown at it, with the exception of the GSP and a G-Major 2. It absolutely despised the G-System that I used to have. It gets along with the GSP1101 very well though.
Sometimes it's just a matter of finding gear that goes together. The only amp that I have had zero problems with ground loops is a Roadking Series 1 that I used to have. It loved everything, but the cleans were terrible and it weighed 108 pounds.
If you are scientific about your setup, you can easily isolate the ground loop, if it is a ground loop.
Between each step, place the amp on Standby so that you don't have any unnecessary pops.
1. Plug your guitar into your amp with nothing else connected to it.
If no hum, move to the next step.
2. Next, plug the FX8 Out into the Return of the amp.
Turn the Standby off and see if you have any hum.
If not, next step.
3. Plug the Amp Send to the FX8 In (Post)
Turn the amp on and see if there is hum.
Play your guitar for a little while.
If no hum, move on.
4. Plug a cable from the FX8 Out (Pre) to the amp's input.
Do not plug your guitar into the FX8 yet.
Turn the amp on and see if there is hum.
If no hum, next step......
5. Plug your guitar into the FX8 Input.
Turn the amp on and play.
These steps will help you isolate where the hum is coming from. It is usually only 1 or 2 connections that are doing it.
The chances of a ground loop can be greatly exaggerated if you are using the Relays to control the amp's switching functions because it is another cord (or 2) that connect the same two devices.
Midi is great because there are opto-isolators in the midi circuit, so the amp and the FX8 are physically disconnected from each other on these cables.
Once you have isolated where the hum comes from, then you can try different cables, isolation transformers, humbuster cables, etc..