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

Ontario Clinical Oncology Group (OCOG)

Status and phase: Completed; Phase 1

Conditions: Acute Myeloid Leukemia

Treatments: Drug: Thioridazine

Study type: Interventional

Funder types: Other

Identifiers

NCT02096289

OCOG-2013-THORIDAL

Details and patient eligibility

About

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.

Enrollment: 13 patients

Sex: All

Ages: 55 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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13 participants in 1 patient group

Thioridazine

Experimental group

Description:

Up to 3 dose levels of thioridazine will be assessed sequentially: 25 mg Q6H (Level I), 50 mg Q6H (Level II) and 100 mg Q6H (Level III). The duration of thioridazine therapy is for a total of 21 days (Days 1-22 on study). All patients will receive cytarabine 1 g/m2 administered as a 2 hour infusion for 5 consecutive days (Days 6-10 on study).

Treatment:

Drug: Thioridazine