The collision happened at roughly 2.30am, with it reported that the vehicle crashed with a CSX Freight train.
Emergency services are at the scene between Charleston Highway and Pine Ridge Road.
Early reports suggests many people are wounded.
A spokesman for Lexington sheriff confirmed in a tweet: “Train collision and derailment near Charleston Highway and Pine Ridge Road.
“More details to come.”
The crash comes only days after another Amtrak train carrying dozens of Republican members of Congress slammed into a garbage truck in rural Virginia.
A passenger on the garbage truck, 28-year-old Christopher Foley, was killed and two others on the truck were injured, according to police.
No poiticians were seriously injured but a Minnesota representative, Jason Lewis, was taken to a hospital as a precaution and released.
The chartered train was travelling at 61 miles per hour when the drive braked before smashing into a truck on the tracks.
The National Transportation Safety Board said in a briefing that the maximum speed limit at the grade crossing was 60 miles per hour and that the engineer in Wednesday’s crash applied the brakes 20 seconds before the train came to rest, according to preliminary information downloaded from one of the train’s event data recorders.
The NTSB is still investigating whether the train braked prior to impact.