Inclusion Criteria - Initial Enrollment:

          -  Participant has a relapsed or refractory hematologic malignancy (with any measurable
             disease) with FLT3-ITD or TKD mutations and one of the following diagnoses:

               -  Acute myeloid leukemia (AML)

               -  AML with prior myelodysplastic syndrome (MDS)

               -  Myeloperoxidase (MPO)-positive mixed phenotype acute leukemia

          -  Participant's disease has relapsed after, is refractory to induction and/or salvage
             therapy, or has relapsed after hematopoietic stem cell transplant (HSCT).

          -  Participant disease tested positive for FLT3-ITD or -TKD within 60-day screening
             period.

          -  Participant's age is 1 to 25 years, inclusive (St. Jude participants must be aged 1 to
             25 years, inclusive).

          -  Karnofsky or Lansky performance score is > 60%. The Lansky performance score should be
             used for participants < 16 years and the Karnofsky performance score for participants
             ≥ 16 years.

          -  Adequate organ function defined as:

               -  Bilirubin ≤1.5 x upper limit of normal (ULN)

               -  ALT ≤ 3 x ULN and AST ≤ 3 x ULN

               -  Serum creatinine ≤1.5 x ULN

          -  Participant must have recovered from the acute side effects of all prior anti-cancer
             therapy, and:

               -  At least 2 weeks have elapsed since prior systemic cytotoxic chemotherapy (except
                  intrathecal chemotherapy, hydroxyurea, low-dose cytarabine, and/or low dose
                  maintenance therapy such as vincristine, mercaptopurine, methotrexate or
                  glucocorticoids), and

               -  If the participant received a prior allogeneic HSCT, at least 30 days have
                  elapsed and there is no evidence of clinically significant graft versus host
                  disease requiring treatment and/or have > grade 2 persistent non-hematologic
                  toxicity related to a transplant

        Exclusion Criteria - Initial Enrollment:

          -  Concurrent chemotherapy, or targeted anti-cancer agents, other than hydroxyurea,
             low-dose cytarabine, intrathecal therapy and/or low dose maintenance therapy such as
             vincristine, mercaptopurine, methotrexate or glucocorticoids.

          -  Patient with concurrent severe and/or uncontrolled medical conditions that, in the
             opinion of the investigator, may impair participation in the study or the evaluation
             of safety and/or efficacy.

          -  Known HIV infection or active hepatitis B (defined as hepatitis B surface
             antigen-positive) or C (defined as hepatitis C antibody-positive).

          -  Prior crenolanib treatment for a non-leukemic indication.

          -  Major surgical procedures within 14 days of Day 1 administration of crenolanib.

          -  Pregnant or lactating (female participant of childbearing potential must have negative
             serum or urine pregnancy test required within 7 days prior to start of treatment).

          -  Male or female participant of reproductive potential must agree to use appropriate
             methods of contraception for the duration of study treatment and for at least 30 days
             after last dose of protocol treatment

          -  Inability or unwillingness or research participant or legal guardian/representative to
             give written informed consent.

        Inclusion Criteria - Maintenance Therapy After HSCT:

          -  Patient must have received crenolanib on this protocol prior to HSCT to continue on to
             maintenance.

          -  Patient must be within 30 - 120 days after hematopoietic stem cell transplant (HSCT).

          -  Response to previous treatment on this protocol: at least resistant disease with
             clinical benefit or better response.

          -  Patient is off or on a stable dose of immunosuppressive drugs for management or
             prophylaxis of graft-versus-host-disease (GVHD) (defined as no escalation of therapy
             for GVHD) within 14 days prior to starting crenolanib.

          -  Patient must have recovered from acute side effects of HSCT, defined as having <Grade
             2 non-hematological toxicity related to the transplant (exceptions are alopecia and
             other non-acute toxicities).

          -  Adequate hematopoietic recovery (ANC >500/mm^3 and platelet count >50,000/mm^3)

          -  Research participant or legal guardian/representative is able and willing to give
             written informed consent.