Phase II Study of Crenolanib in Subjects With Relapsed AML With FLT3-D835 Activating Mutations

Inclusion Criteria:

• Relapsed primary AML or AML secondary to myelodysplastic syndrome with an expected survival of 3 months or greater
• Presence of a FLT3-D835 activating mutation irrespective of presence of other mutations like FLT3-ITD
• Age ≥18 years
• ECOG PS 0 - 2
• Adequate liver function, defined as total or direct bilirubin ≤1.5x ULN, ALT ≤3.0x ULN, AST ≤3.0x ULN. Exceptions for ALT and AST restrictions will be made in the setting of documented liver involvement with leukemia.
• Adequate renal function, defined as serum creatinine ≤1.5x ULN
• Recovery from non-hematological toxicities of prior therapy (including HSCT) to no more than grade 1 (except alopecia)
• In the absence of rapidly progressing leukemia, subjects should have received no anti-leukemic therapy (except hydroxyurea) for 2 weeks (for classical cytotoxic agents and FLT3 inhibitors; 4 weeks for radiation) prior to first dose of crenolanib.
• Negative pregnancy test for women of childbearing potential.
• Able and willing to provide written informed consent.

Exclusion Criteria:

• Absence of FLT3-D835 activating mutation
• <5% blasts in blood or marrow at screening
• Concurrent chemotherapy, systemic immunosuppressants, or targeted anti-cancer agents, other than hydroxyurea.
• Patient with concurrent severe and/or uncontrolled medical conditions that in the opinion of the investigator may impair the participation in the study or the evaluation of safety and/or efficacy.
• HIV infection or active hepatitis B or C
• Subjects who have had HSCT and are within 60 days of an allogeneic or autologous transplant, and/or have clinically significant graft-versus-host disease requiring systemic treatment.
• Unwillingness or inability to comply with protocol.