study of ff-10101-01 in patients with relapsed or refractory acute myeloid leukemia

Conditions: AML, Adult

Summary: a phase 1 dose escalation and dose ranging study of ff-10101-01 in subjects with relapsed or refractory acute myeloid leukemia to determine the safety, tolerability, pk and preliminary efficacy. a total of 9 cohorts will be enrolled in phase 1 to establish the maximum tolerated dose (mtd).

subjects will receive ff-10101-01 orally once a day repeated every 28 days =1 cycle frequent blood draws will be collected to measure pharmacodynamic parameters and pharmacodynamic activity. disease assessments, including bone marrow aspirates, will be performed at the beginning of cycles 1-3, and every 3 months thereafter. subjects who demonstrate objective response or stable disease will be allowed to continue therapy with ff-10101-01 until , observation of unacceptable adverse events, or until the subject is no longer deriving benefit based on the opinion of the investigator.

Eligibility criteria:
subjects who are able and willing to give written informed consent * documented primary or secondary aml, as defined by the who criteria (2008), by histopathology refractory to previous induction chemotherapy and/or relapsed after achieving remission with a prior chemotherapy and who are not candidates for other available therapy likely to confer clinical benefit. * eastern cooperative oncology group (ecog) performance status of 0 to 2 * in the absence of rapidly progressing disease, the interval from prior treatment to time of ff-10101-01 administration should be at least 14 days for cytotoxic agents other than hydroxyurea, at least 5 half-lives for non-cytotoxic agents, and 14 days for monoclonal antibody therapies. hydroxyurea may be continued for a maximum of 14 days from the start of ff-10101-01 dosing, through cycle 1 day 14, with a maximal dose of 5 grams/day * persistent chronic clinically significant toxicities from prior chemotherapy or surgery must be ≤grade 2 * if subject has had a hematopoietic stem cell transplant, subject must be ≥60 days post-transplant with no clinically significant gvhd requiring systemic therapy * alanine aminotransferase (alt) and/or aspartate aminotransferase (ast) ≤3 times the upper limit of normal and total bilirubin of ≤1.5x the upper limit of normal. if total bilirubin is equal to or exceeds 1.5x the upper limit of normal, the subject can still be included if direct bilirubin is ≤1.5x the upper limit of normal * calculated creatinine clearance of ≥60 ml/min * female subjects of childbearing potential and sexually mature male subjects must agree to use a medically accepted method of contraception other than an oral contraceptive for the duration of the study. exclusion criteria: * subjects diagnosed with acute promyelocytic leukemia * subjects with bcr-abl positive leukemia (chronic myelogenous leukemia in blast crisis) * subjects with clinically active cns leukemia * subjects with major surgery within 28 days prior to the first administration of ff-10101-01 * subjects with radiation therapy within 28 days prior to the first administration of ff-10101-01 * subjects with active malignant disease requiring therapy other than aml or myelodysplastic syndrome with transformation into aml * subjects with an active uncontrolled infection * subjects with a medical condition, serious intercurrent illness, or other circumstance that, in the investigator's judgment, could jeopardize the subject's safety as a study subject, or that could interfere with the study objectives * subjects known to have human immunodeficiency virus infection, or who have active hepatitis b or c infection as determined by serological testing * subjects with congestive heart failure, new york heart association (nyha) class 3 or 4, or subjects with a past history of congestive heart failure nyha class 3 or 4 and in whom echocardiogram or multiple gate acquisition (muga) scan performed within 3 months prior to screening or at screening showed a lvef \<40% * female subjects who are pregnant or breast feeding * subjects on 3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors (statins) or other drugs known to have muscle toxicity * subjects taking strong inhibitors of cyp3a4 will be excluded from the study unless therapeutic substitution is possible * subjects taking strong inducers of cyp3a4 will be excluded from the study unless therapeutic substitution is possible * use of systemic immunosuppressive agents within 14 days prior to first dose of ff-10101 * subjects taking drugs known to cause torsades de pointes will be excluded from the study unless therapeutic substitution is possible * subjects known to have long qt syndrome * subjects with mean qtcf values following 3 ecgs conducted 5 minutes apart of \>470 msec

Keywords: acute myeloid leukemia