Pedro Porro, Rodrigo Bentancur, Palhinha and Wilson Odobert are the only players to retain a starting role for Tottenham following Saturday's 2-2 draw at Brighton.
Goalkeeper Antonin Kinsky makes his first start of the season with Kevin Danso, Xavi Simons, Mathys Tel, Archie Gray, Brennan Johnson and Djed Spence also coming in.
Tottenham XI: Kinsky, Danso, Porro, Spence, Gray, Bentancur, Palhinha, Simons, Odobert, Tel, Johnson.
Subs: Austin, Richarlison, Udogie, Bergvall, Van de Ven, Scarlett, Thompson, Byfield, Williams-Barnett.
League One Doncaster have already pulled off an upset in this season's Carabao Cup - beating Championship side Middlesbrough - and boss Grant McCann makes nine changes after losing against AFC Wimbledon on Saturday.
Centre-back Jay McGrath and midfielder Owen Bailey are the only two to hold on to their starting berth.
Damola Ajayi is on loan from Tottenham but has been given permission to feature against his parent club.
Doncaster XI: Lawlor, Bailey, McGrath, Sbarra, Nixon, Middleton, Ajayi, Senior Grehan, Olusanya, Close.