 She married Theodore Palaiologos in Mystras on January 21, 1421, or sometime in 1422 in an arranged marriage that was part of an initiative of her uncle, Pope Martin V, to join Western (Roman Catholic) with Orthodox nobility, who in this way hoped to gain political alliances against the Ottoman Turks.On the 20th of August 1420, Cleofa left Italy embarking from Fano near Pesaro for Constantinople.She was accompanied by another young bride, Sophia of Montferrat, who was to marry John VIII Palaiologos, Theodore's brother.