A Phase II Study of Crenolanib Besylate in Subjects with Relapsed Acute Myeloid Leukemia with FLT3-D835 Activating Mutations
The study will enroll AML patients with FLT3 D835 activating mutations. Patients will be treated with crenolanib (100 mg, three times daily) continuously until they fulfill one of the criteria for study discontinuation.
Fourteen AML patients with FLT3 D835 activating mutations will be treated with 100 mg of crenolanib three times daily until they meet one of the criteria for discontinuation. Subject efficacy evaluations will be performed at scheduled time points. These include: monthly bone marrow biopsy for two months, and then every three months for as long as criteria for CRc is maintained. At loss of CRc, bone-marrow biopsy will be performed only as clinically indicated to exclude toxicity issues such as myelosuppression from progressive AML. Subjects[Right Quote] best clinical response will be recorded, as well as the response at 2 months. Subjects not in CR by the end of month 2 but showing clinical benefit will be allowed to continue therapy at the discretion of the physician.
•Relapsed primary AML or AML secondary to antecedent hematologic disorder 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)
•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.
*Subjects who received crenolanib prior to and are within 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 been escalated within 14 days prior to start of study drug.