safety study of thioridazine in combination with cytarabine to treat relapsed or refractory acute myeloid leukemia

Conditions: Acute Myeloid Leukemia

Summary: this is a phase i trial investigating the safety of using thioridazine in addition to cytarabine in elderly patients with relapsed or refractory acute myeloid leukemia.


Eligibility criteria:
inclusion criteria: * have a diagnosis of aml according to the who classification1 * aml is refractory or relapsed (requiring at least 5% leukemic blasts in the bone marrow, regardless of the presence of other features such as new or recurrent dysplastic changes or extra medullary disease) according to the following definitions: * relapsed (defined as ≥ 5% leukemic blasts in the bone marrow) after three months from receiving up to three prior induction regimens. * refractory (defined as ≥ 5% leukemic blasts in the bone marrow) to not more than one prior induction regimen (defined as failure to achieve a cr or cri following induction therapy). * 55 years of age or older. exclusion criteria: * receiving any other systemic anti-leukemic therapy (standard or investigational). * having received more than two prior chemotherapy lines for aml. induction/consolidation therapy and bone marrow transplant are each considered a line of therapy. * having received previous aml therapy within four weeks of the first dose of study drug, with the exception of hydroxyurea. * clinical evidence suggestive of cns involvement with leukemia unless a lumbar puncture confirms the absence of leukemic blasts in the csf. * acute promyelocytic leukemia. * an ecog performance status of 3 or more. * inadequate renal function (i.e., estimated gfr \< 60 ml/min/1.73m2). * inadequate hepatic function (i.e., serum bilirubin \> 1.5×uln; ast, alt and alkaline phosphatase \> 2.5×uln). * presence of acute or chronic gvhd. * presence of a systemic fungal, bacterial, viral or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment). * having any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver or other organ system that may place the patient at undue risk to undergo induction therapy. * diagnosed with a condition that can prolong the qt interval (e.g., long qt syndrome) or have a qtc interval ≥ 470ms if male, or ≥ 480ms if female. * left ventricular ejection fraction less than 45%. * history of uncontrolled cardiac arrhythmia. * known severe hypotensive or hypertensive heart disease. * prior malignancy, unless the patient has been disease-free for at least five years following curative intent therapy, with the following exceptions: patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, if definitive treatment for the condition has been completed; or patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (psa) values if hormonal therapy has been initiated or a radical prostatectomy has been performed. * known hiv positivity. * known pregnancy or lactating female. * presence of a psychiatric disorder that would interfere with consent, study participation, or follow-up. * unable to provide informed consent.

Keywords: relapsed acute myeloid leukemia refractory acute myeloid leukemia thioridazine phase i clinical trial