Phase I, Open-label, Dose-escalation Study of the Combination of Sorafenib and Vorinostat in Poor-risk Acute Myelogenous Leukemia (AML) and High Risk Myelodysplastic Syndrome (MDS)
- Patients must have a diagnosis of AML (> 20% myeloid blasts in the peripheral blood
or bone marrow) or MDS with > 10% myeloid blasts in the bone marrow. Patients with
Acute Promyelocytic Leukemia (APL) must be refractory to all-trans retinoic acid
(ATRA) and arsenic trioxide.
- The patients must have one of the following criteria:
- Age of 18 to 69 years; relapsed or refractory disease following at least one
prior therapeutic regimen; not a candidate for cytotoxic or other conventional
therapies due to disease refractoriness, poor performance status, or
- Age of 70 years or older; received no previous therapies (other than
hematopoietic growth factors or hydroxyurea); not a candidate for cytotoxic or
other conventional therapies due to poor performance status, co-morbidities, or
- Age of 70 years or older with relapsed or refractory disease
- The patient must have discontinued all previous therapies for acute leukemia for at
least 14 days and recovered from the acute effects of the therapy.
- Patients must have an ECOG (Zubrod) performance status of 0-2
- Patients must be able to take and tolerate oral medications
- Patients must have adequate organ function as specified in the protocol.
- Patients not on anti-coagulation must have an INR < 1.5 and a PTT within normal
- Pregnant women or nursing mothers are not eligible for this trial.
- Patients may receive no other concurrent biologic therapy, cytotoxic chemotherapy or
radiation therapy during this trial.
- Patients with one or more serious preexisting medical conditions that, in the opinion
of the investigator, would preclude participation in this study. See protocol for
- Patients with known central nervous system (CNS) leukemia by spinal fluid cytology,
flow cytometry or imaging
- Patients with previous autologous or allogeneic stem cell transplantation who have
current side effects and/or complications that in the opinion of the investigator can
interfere with the interpretation of the toxicities.