Crenolanib in Combination With Sorafenib in Patients With Refractory or Relapsed Hematologic Malignancies

"Day 1 of Course 1: once followed by pharmacokinetic analysis. Days 2-28 of cycle 1: 3 times per day Crenolanib dose will not be adjusted unless the participant experiences side effects.~All subsequent courses: 3 times per day on Days 1-28. At least 50% of participants in each dose level must be ≤ 18 years old."

"Days 8-28 of course 1: given orally once each day.~All subsequent courses: given orally on days 1-28 once per day~This is a dose-finding study for the use of sorafenib in combination with crenolanib. Different doses will be given to several participants, with the first participants receiving a lower dose than typically used in children as a single agent. If the drug does not cause serious side effects, it will be given to other study participants at a higher dose. If side effects occur, the dose will be lowered."

Triple IT therapy includes methotrexate, hydrocortisone and cytarabine with leucovorin rescue given on day 8. All participants will receive one IT chemotherapy on Day 8 of the first cycle. If they do not have leukemia cells in their spinal fluid, they will receive only one IT chemotherapy per cycle. If leukemia cells are present in their spinal fluid, they will receive IT chemotherapy weekly during the course. Triple IT therapy will be repeated on Day 1 of Cycle 2 and with each subsequent cycle in all participants.