Phase II Study of Crenolanib in Subjects With Relapsed/Refractory AML With FLT3 Activating Mutations

Inclusion criteria

• Relapsed/refractory primary AML or AML secondary to antecedent hematologic disorder with an expected survival of 3 months or greater
• Patients must have tested positive for FLT3-ITD and /or other FLT3 activating mutations within < 60 days of the screening period.
• 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)
• Subjects should have received no anti-leukemic therapy (except hydroxyurea) prior to the first dose of crenolanib as follows: for 14 days for classical cytotoxic agents and for five times the t1/2 (half-life) for FLT3 inhibitors and antineoplastic agents that are neither cytotoxic nor FLT3 inhibitors (e.g. hypomethylating agent or MEK inhibitor)
• Negative pregnancy test for women of childbearing potential
• Able and willing to provide written informed consent
• Subjects who received crenolanib prior to and are within 30-90 days of an allogeneic stem cell transplant (HSCT) and have either no active GVHD where therapy has been initiated or GVHD where therapy has not been escalated within 14 days prior to start of study drug

Exclusion criteria

• Absence of FLT3 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 manifested as hepatitis surface antigen positive (HepBsAg) or hepatitis C manifested as hepatitis C antibody positive
• For post HSCT, subjects who are within 29 days of an allogeneic transplant, and/or are on an unstable dose of immunosuppressive drugs for management or prophylaxis of GVHD or have escalated therapy for GVHD within 14 days of starting study drug and/or have >/=Grade 2 persistent non hematological toxicity related to the transplant or did not receive crenolanib prior to HSCT
• Evidence of lack of engraftment if post allogeneic transplant
• Unable to swallow pills
• Major surgical procedures within 14 days of Cycle 1 Day 1 administration of crenolanib
• Unwillingness or inability to comply with protocol.