Study of Crenolanib in Combination Combination With Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia and Activating FLT3 Mutations

The main trial is a double-blinded, placebo-controlled, randomized, phase III, multi-center trial in adult patients with relapsed or refractory AML harboring an activating FLT3 mutation as defined in the inclusion /exclusion criteria.

An initial safety run-in phase of the study will be performed in an open- label administering the study drug crenolanib with salvage chemotherapy consisting of mitoxantrone and cytarabine (MC) in 12 patients according to the experimental arm of the study. After completion of this safety run-in phase, toxicity and response data will be provided to the external Data and Safety Monitoring Board (DSMB) and the Trial- Committee by the Coordinating Investigator. The Trial Committee will decide on the basis of these data and the recommendation of the DSMB on dose- modification and the further conduct of the study with regard to the double-blinded, placebo-controlled, randomized phase of the study.

The double-blinded, placebo-controlled randomized portion will start after the completion of the safety run-in phase and positive opinion of the Trial Committee.

Crenolanib starts on day 7 of MC and is given continuously thereafter, except for days of chemotherapy; if receiving allogeneic HSCT, crenolanib is held during conditioning and transplant and restarts no sooner than 30 days after transplant.

Sample size randomized phase: 276 patients

Primary objective: To evaluate the impact of crenolanib given in combination with salvage chemotherapy and consolidation including allogeneic hematopoietic stem cell transplantation and ongoing single agent maintenance therapy with crenolanib on event-free (EFS) and overall survival (OS) in adult patients with relapsed or refractory AML harboring FLT3 activating mutations.