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

NCT ID: NCT02096289

Last Updated: 2016-12-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-31
• Study Completion Date: 2016-09-30

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Thioridazine

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).

Group Type: EXPERIMENTAL

Thioridazine

Intervention Type: DRUG

Interventions

Thioridazine

Intervention Type: DRUG

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.

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hamilton Health Sciences Corporation

OTHER

Sponsor Role: collaborator

Juravinski Cancer Centre Foundation

OTHER

Sponsor Role: collaborator

Ontario Clinical Oncology Group (OCOG)

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark N Levine, MD

Role: STUDY_DIRECTOR

Ontario Clinical Oncology Group, McMaster University

Ronan Foley, MD

Role: PRINCIPAL_INVESTIGATOR

Hamilton Health Sciences, McMaster University

Locations

Juravinski Hospital & Cancer Centre

Hamilton, Ontario, Canada

Countries

Canada

References

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.

Reference Type: DERIVED

PMID: 30093531 (View on PubMed)

Other Identifiers

OCOG-2013-THORIDAL

Identifier Type: -

Identifier Source: org_study_id