Acute Myeloid LeukemiaPhase 1THORIDALNCT02096289
Safety Study of Thioridazine in Combination With Cytarabine to Treat Relapsed or Refractory Acute Myeloid Leukemia
A Phase 1 study testing Thioridazine in people with Acute Myeloid Leukemia, run by Ontario Clinical Oncology Group (OCOG) at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 55 to 80 years
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Thioridazine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteCanada
- Study dates
- Jul 2014to Sep 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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 locations and contacts
1 site in 1 country.
About this study
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
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
- Being tested
- Thioridazine
- Keywords
- Relapsed Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia, Thioridazine, Phase I, Clinical Trial
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ThioridazineDrug
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: Thioridazine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety
Both acute and late toxicities will be determined according to NCI-CTCAE version 4.03
Measured: Up to 36 days
Secondary outcomes (4)
Assessment of Functional Leukemia Stem Cells
Bone marrow and peripheral blood samples obtained from patients treated with thioridazine and cytarabine will be analyzed in four separate assays.
Measured: Up to 36 days
Pharmacokinetic Analysis of Thioridazine Serum Trough Levels
Pharmacokinetic modeling will be performed to estimate values for individual C min levels.
Measured: Up to 36 days
Assessment of Objective Tumor Response
Tumor responses are categorized as either a complete remission, a complete remission with incomplete count recovery, a partial remission, a treatment failure, or as not evaluable
Measured: Up to 36 days
Pharmacogenetic Analysis of Thioridazine Serum Trough Levels
Cytochrome P450 2D6 genotype will be determined to examine genetic contribution to thioridazine Cmin levels.
Measured: Up to 36 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2014 (estimated)
- Study startJul 2014
- Primary completionAug 2016
- Study completionSep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ontario Clinical Oncology Group (OCOG)
- Sponsor type
- University, hospital or other
- Collaborators
- Hamilton Health Sciences Corporation, Juravinski Cancer Centre Foundation
- Responsible party
- Sponsor
- Investigators
- Mark N Levine, MD, Study director, Ontario Clinical Oncology Group, McMaster UniversityRonan Foley, MD, Principal investigator, Hamilton Health Sciences, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02096289
- Sponsor's protocol ID
- OCOG-2013-THORIDAL
- Acronym
- THORIDAL
- Status last verified
- Dec 2016
- First submitted
- 20 Mar 2014
- Last updated
- 7 Dec 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 30093531
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02096289
- Acronym / sponsor ID
- THORIDAL / OCOG-2013-THORIDAL
- Conditions
- Acute Myeloid Leukemia
- Keywords
- Relapsed Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia, Thioridazine, Phase I, Clinical Trial
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Ontario Clinical Oncology Group (OCOG)University, hospital or other
- Collaborators
- Hamilton Health Sciences Corporation, Juravinski Cancer Centre Foundation
- Study start
- Jul 2014
- Primary completion
- Aug 2016 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 26 Mar 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Thioridazine | Experimental | Drug: ThioridazineUp 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). |
Who may qualify
- Ages
- 55 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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:
- 55 years of age or older.
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Thioridazine | Drug | Thioridazine |
Primary outcome
Safety
Time frame: Up to 36 days
Both acute and late toxicities will be determined according to NCI-CTCAE version 4.03
4 secondary outcomes
Assessment of Functional Leukemia Stem Cells
Time frame: Up to 36 days
Pharmacokinetic Analysis of Thioridazine Serum Trough Levels
Time frame: Up to 36 days
Assessment of Objective Tumor Response
Time frame: Up to 36 days
Pharmacogenetic Analysis of Thioridazine Serum Trough Levels
Time frame: Up to 36 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Dec 2016.
- Derived from this study: PubMed 30093531Aslostovar 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark N Levine, MD study director
Ontario Clinical Oncology Group, McMaster University
Ronan Foley, MD principal investigator
Hamilton Health Sciences, McMaster University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Thioridazine in people with Acute Myeloid Leukemia, run by Ontario Clinical Oncology Group (OCOG) at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety (time frame: Up to 36 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02096289, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Dec 2016.