Safety Study of Thioridazine in Combination With Cytarabine to Treat Relapsed or Refractory Acute Myeloid Leukemia

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.