Ukrainian President Volodymyr Zelenskyy on Tuesday dismissed his deputy chief of staff Rostyslav Shurma, according to a decree on the presidential website.
MPs and political analysts have expected major changes in the government since summer began.
The exit of the three ministers adds to the uncertainty around the government with at least five other ministerial portfolios vacant after sackings earlier this year.
Zelenskyy and his political team could move to fill all the positions now in a bid to bring in order before he travels to the United States this month to attend the United Nations General Assembly.
The Ukrainian leader said last week that he hoped to have a meeting with US President Joe Biden and his two possible successors to present a “victory plan” that would coerce Russia into ending its war in Ukraine.
Ukraine’s first lady said on Tuesday at least 47 people were killed and 206 wounded when Russia struck a military institute in the central town of Poltava with two missiles.
Emergency services gave the death toll of 50; other officials said 51 were killed.
A further 15 people may still be under the rubble, according to Poltava regional governor Filip Pronin.
Photographs posted on social media showed several bodies lying on the ground covered in dust and debris, with the badly damaged side of a large building behind them.
Reuters could not immediately verify the images.
“The Russian scum will definitely be held accountable for this strike,” Zelenskyy said on the Telegram messaging app.
He ordered a full and prompt investigation, saying the strike with two ballistic missiles damaged a building of the Military Institute of Communications.
It was not immediately clear who the victims were.
Ukrainian military bloggers suggested some might be cadets or recently mobilised men undergoing training.
The use of ballistic missiles - which hit targets hundreds of kilometres away within a few minutes of their launch - meant the victims had almost no time to find cover after the air raid siren sounded, the foreign ministry said.
“This is a stunning tragedy for all of Ukraine. The enemy hit an educational institution and a hospital,” Ukraine’s first lady Olena Zelenska wrote on X.
Some Ukrainians left worried messages on the institute’s Facebook page seeking information about their loved ones.
“One of the institute’s buildings was partially destroyed, and many people were trapped under the rubble,” the defence ministry said on Telegram.
“Thanks to the co-ordinated work of rescuers and medics, 25 people were rescued, 11 of whom were taken from the rubble. The rescuers are currently continuing their work.”
Russia did not immediately comment on the attack.
In Poltava, 300km southeast of Kyiv and 120km to the nearest Russian border, governor Filip Pronin said that many residents had donated blood for the wounded.
Local authorities announced three days of mourning.
Serhiy Beskrestnov, a prominent Ukrainian Telegram blogger followed by many radio, communications and electronic warfare specialists in Ukraine’s military, posted a tribute to “my signals operator comrades”.
Fighting has intensified over the past month, with Russian forces advancing in heavy battles in eastern Ukraine while Ukrainian troops have mounted their first large-scale cross-border assault into a Russian region, for which Russia has vowed to retaliate.
