A Pilot Study of Sorafenib in Patients with Acute Myeloid Leukemia as Peri-Transplant Remission Maintenance
Determine the toxicity and safety of incorporation of Sorafanib into the pre or post transplant maintenance setting for three types of transplants. Toxicity as well as the clinical failures of graft versus host disease and graft failure will be monitored continuously throughout the trial.
Inclusion criteria(must meet both 1 & 2) 1)Acute Myeloid leukemia with a FLT3 ITD who are eligible to undergo a bone marrow transplant as a form of remission consolidation are eligible for enrollment 2)Patients with documented complete or partial remissions who have had count recovery (ANC over 500, non transfused platelet count over 50) and are at least 30 post induction or transplantation but no more than 120 days post transplant. Exclusion criteria 1)Lack of engraftment as evidenced by restriction fragment length polymorphism(RFLP) 2)Patients with active CNS disease 3)Patients with active infection 4)Patients with active acute GVHD with GVHD therapy initiation or escalation within 21 days Age greater than 18 years. Patients must have normal organ and marrow function as defined below: -total bilirubinLess than 2x upper limit of normal -AST(SGOT)/ALT(SGPT) less than 5 X institutional upper limit of normal -creatinine within normal institutional limits OR -creatinine clearance greater than 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
Oral sorafenib at 200mg twice daily with dose escalation for tolerance. Dose reduction for Grade 3 toxicities. Start of therapy would occur within 14 days of assessment of remission status (~day 30). If remission is documented and bone marrow transplant prep will occur on or before day 65, patients will proceed directly to bone marrow transplant. For patients who will go to transplant after day 65, patients will receive oral sorafenib at 200mg twice daily(dose level 1) for a minimum of seven days, if tolerated well, patients may dose escalate to dose level 2 at the discretion of the clinician. Oral sorafenib will be continued until four days prior to start of transplant prep. Sorafenib will restart at the time of engraftment but no later than 120 days post transplant. For those patients with evidence of partial response at the time of induction response assessment, patients may start sorafenib at the MTD of 400mg BID at the discretion of the clinician.
12/20/2013 04:02 AM