In the Onchange property of HomeCenter combobox ,you can set a context variable like
UpdateContext({homecenter_changed:true});
and set the value of the same variable as false in the page OnVisible property as
UpdateContext({homecenter_changed:false});
Set the Items property of Supervisor ComboBox as
If(homecenter_changed = true,Filter(Issue Tracker,Home Center =HomeCenter_combobox.Selected.Home Center).Supervisor)
Similarly,the Items property of Regional Manager can be set as
If(homecenter_changed = true,Filter(Issue Tracker,Home Center =HomeCenter_combobox.Selected.Home Center).Regional Manager)
And in the OnChange property of both Supervisor and Regional Manager,update the context varaible back to false,then only the next time you change the value for Home Center,the other two values gets autopopulated properly,like
UpdateContext({homecenter_changed:false});