Clinical trial NCT02096289: Safety Study of Thioridazine in Combination With Cytarabine to Treat Relapsed or Refractory Acute Myeloid Leukemia
Official title: A Phase I Trial Evaluating Oral Thioridazine in Combination With Intermediate Dose Cytarabine in Patients 55 Years and Older With Acute Myeloid Leukemia Who Have Relapsed or Have Refractory Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Keywords: Relapsed Acute Myeloid Leukemia
Refractory Acute Myeloid Leukemia
Thioridazine
Phase I
Clinical Trial
Lead sponsor: Ontario Clinical Oncology Group (OCOG)
Sponsor class: OTHER
Collaborators: name: Hamilton Health Sciences Corporation
name: Juravinski Cancer Centre Foundation
First posted: 2014-03-26
Enrollment: 13
Sex: ALL
Minimum age (years): 55
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Safety
timeFrame: Up to 36 days
Secondary outcomes:
measure: Assessment of Functional Leukemia Stem Cells
timeFrame: Up to 36 days
measure: Pharmacokinetic Analysis of Thioridazine Serum Trough Levels
timeFrame: Up to 36 days
measure: Assessment of Objective Tumor Response
timeFrame: Up to 36 days
measure: Pharmacogenetic Analysis of Thioridazine Serum Trough Levels
timeFrame: Up to 36 days
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: Juravinski Hospital & Cancer Centre
state: Ontario
Study officials:
affiliation: Ontario Clinical Oncology Group, McMaster University
name: Mark N Levine, MD
role: STUDY_DIRECTOR
affiliation: Hamilton Health Sciences, McMaster University
name: Ronan Foley, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Aslostovar L, Boyd AL, Almakadi M, Collins TJ, Leong DP, Tirona RG, Kim RB, Julian JA, Xenocostas A, Leber B, Levine MN, Foley R, Bhatia M. A phase 1 trial evaluating thioridazine in combination with cytarabine in patients with acute myeloid leukemia. Blood Adv. 2018 Aug 14;2(15):1935-1945. doi: 10.1182/bloodadvances.2018015677.