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

NCT02096289 | Completed Phase 1

• 1 other identifier: OCOG-2013-THORIDAL
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Myeloid Leukemia

Keywords

Relapsed Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia; Thioridazine; Phase I; Clinical Trial

Outcome Measures

Primary Outcomes (1)

• Safety

  Both acute and late toxicities will be determined according to NCI-CTCAE version 4.03

  Up to 36 days

Secondary Outcomes (4)

• Assessment of Functional Leukemia Stem Cells

  Up to 36 days

• Pharmacokinetic Analysis of Thioridazine Serum Trough Levels

  Up to 36 days

• Assessment of Objective Tumor Response

  Up to 36 days

• Pharmacogenetic Analysis of Thioridazine Serum Trough Levels

  Up to 36 days

Study Arms (1)

Thioridazine

EXPERIMENTAL

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).

Drug: Thioridazine

Interventions

Thioridazine DRUG

Thioridazine

Eligibility Criteria

• Age: 55 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• years of age or older.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ontario Clinical Oncology Group (OCOG): lead
• Hamilton Health Sciences Corporation: collaborator
• Juravinski Cancer Centre Foundation: collaborator

Study Sites (1)

Juravinski Hospital & Cancer Centre

Hamilton, Ontario, L8V 1C3, Canada

Location

Related Publications (1)

• 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.

  PMID: 30093531 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Thioridazine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Phenothiazines; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Mark N Levine, MD

  Ontario Clinical Oncology Group, McMaster University

  STUDY DIRECTOR

• Ronan Foley, MD

  Hamilton Health Sciences, McMaster University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2014
• First Posted: March 26, 2014
• Study Start: July 1, 2014
• Primary Completion: August 1, 2016
• Study Completion: September 1, 2016
• Last Updated: December 7, 2016

Record last verified: 2016-12

Locations

CA (1)