A Phase II Study of Crenolanib Besylate in Subjects with Relapsed/Refractory Acute Myeloid Leukemia with FLT3 Activating Mutations
The study will enroll fourteen relapsed/refractory aML patients with FLT3 activating mutations. Subjects will be treated with crenolanib daily as reinduction until they meet one of the criteria for discontinuation. after HCST, patients who received crenolanib prior to transplant and achieved resonse may continue on study post-transplant with maintenance ccrenolanib 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 in the first two months, and then every three months for as long as criteria for CR/CRi is maintained. at loss of CR/CRi, bone-marrow biopsy will be performed only as clinically indicated to exclude toxicity issues such as pancytopenia due to study drug versus myelosuppression from progressive aML. Subjects' best clinical response will be recorded, as well as the response at 2 months. Subjects not in CR/Cri 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
* 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 x 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.