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Study Evaluating the Tolerance and Biological Activity of Oral Clioquinol in Patients With Relapsed or Refractory Hematological Malignancy

Primary Purpose

Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, Chronic Lymphocytic Leukemia

Status
Terminated
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
Clioquinol
Sponsored by
University Health Network, Toronto
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring clioquinol, relapsed and refractory hematologic malignancy, ALL, HD, CLL, High risk myelodysplasia (MDS) with an IPSS score >2.5, CML blast crisis, Relapsed or refractory acute myeloid leukemia (AML)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Relapsed or refractory acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), high risk myelodysplasia (MDS) with an IPSS score > 2.5, Non-Hodgkin's lymphoma (NHL), Hodgkin's lymphoma (HD) or multiple myeloma, for which all potentially curative or standard salvage therapy options have been exhausted.
  2. ECOG performance status < 2.

  3. Biochemical values within the following range:

    • Serum creatinine < 2x upper limit of normal.
    • Total bilirubin < 2x upper limit of normal, AST and ALT < 5x upper limit of normal.
    • Normal serum B12 level.
  4. Ability to maintain adequate oral intake of medication.
  5. Ability to understand and sign informed consent.
  6. Toxicity from prior chemotherapy has resolved.

Exclusion Criteria:

  1. Uncontrolled systemic infection.
  2. Uncontrolled intracurrent illness.
  3. Pregnant or breast feeding.
  4. CNS disease.
  5. Neurologic symptoms related to intracurrent illnesses or unexplained causes.
  6. Psychiatric illness that would limit compliance with study.
  7. Receiving other systemic chemotherapy, other than hydroxyurea to control circulating blast counts, within 10 days of study entry. Hydroxyurea is permitted, however the dose must be stable and unchanged in the 7 days prior to initiation with Clioquinol.
  8. Prior therapy with Clioquinol.
  9. Use of other investigational antileukemic therapy within two weeks of study entry.
  10. Given the neurological side of Clioquinol in the Japanese population, this population, this trial will exclude patients who have a parent of Oriental or Japanese origin or who self-identify as Oriental or Japanese (Appendix 9.2).
  11. Active ocular problems including visual migraines and glaucoma.
  12. Use of oral or intravenous heavy metal supplements including copper, zinc, and nickel.

Sites / Locations

  • Princess Margaret Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Clioquinol

Arm Description

Patients will take Clioquniol at various doses depending on which dose level they come into the study at. Once a MTD has been determined, the new patients that enter into the trial will then take it at that level.

Outcomes

Primary Outcome Measures

To evaluate the dose-limiting toxicity (DLT), maximum tolerated dose, and recommended phase II dose. To partially characterize the pharmacokinetics of Clioquinol in plasma following single and multiple oral dosing.

Secondary Outcome Measures

To determine the pharmacodynamic effects of Clioquinol on activity of the proteasome and relationship to the steady-state plasma concentrations of Cliquinol following multiple dosing, and to determine the response rate of Cliquinol.

Full Information

First Posted
August 19, 2009
Last Updated
June 19, 2015
Sponsor
University Health Network, Toronto
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1. Study Identification

Unique Protocol Identification Number
NCT00963495
Brief Title
Study Evaluating the Tolerance and Biological Activity of Oral Clioquinol in Patients With Relapsed or Refractory Hematological Malignancy
Official Title
Phase 1 Study Evaluating the Tolerance and Biological Activity of Oral Clioquinol in Patients With Relapsed or Refractory Hematological Malignancy
Study Type
Interventional

2. Study Status

Record Verification Date
June 2015
Overall Recruitment Status
Terminated
Study Start Date
August 2009 (undefined)
Primary Completion Date
September 2013 (Actual)
Study Completion Date
September 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Health Network, Toronto

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is an open-label, single arm phase 1 study to evaluate the dose-limiting toxicity, maximum tolerated dose, and recommended phase II dose of Clioquinol in patients with relapsed or refractory hematologic malignancies. The study will also characterize Cliquinol's safety, tolerability and pharmacodynamic effect.
Detailed Description
This is an open-label, single arm study. Approximately 4-48 patients will be enrolled. Patients will receive 800mg/day of Clioquinol at the start of the trial and the dose will be increased by 800mg with each subsequent level until the MTD is determined. Patients will then increase their frequency of the drug. Response to Clioquinol will be determined on day 21 for the 8 and 15 day dosing schedule and on day 28 for the 22 day dosing schedule ( 1 cycle). Patients who have demonstrated a response to the drug will be eligible to receive up to 5 additional cycles at the same dose and frequency every 21 days.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, Chronic Lymphocytic Leukemia, Myelodysplasia, Lymphoma, Non-Hodgkin, Hodgkin's Lymphoma, Multiple Myeloma
Keywords
clioquinol, relapsed and refractory hematologic malignancy, ALL, HD, CLL, High risk myelodysplasia (MDS) with an IPSS score >2.5, CML blast crisis, Relapsed or refractory acute myeloid leukemia (AML)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
11 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Clioquinol
Arm Type
Experimental
Arm Description
Patients will take Clioquniol at various doses depending on which dose level they come into the study at. Once a MTD has been determined, the new patients that enter into the trial will then take it at that level.
Intervention Type
Drug
Intervention Name(s)
Clioquinol
Intervention Description
Patients will take Clioquniol at escalating doses depending on when they enter into the trial.
Primary Outcome Measure Information:
Title
To evaluate the dose-limiting toxicity (DLT), maximum tolerated dose, and recommended phase II dose. To partially characterize the pharmacokinetics of Clioquinol in plasma following single and multiple oral dosing.
Time Frame
Varies
Secondary Outcome Measure Information:
Title
To determine the pharmacodynamic effects of Clioquinol on activity of the proteasome and relationship to the steady-state plasma concentrations of Cliquinol following multiple dosing, and to determine the response rate of Cliquinol.
Time Frame
Varies

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Relapsed or refractory acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), high risk myelodysplasia (MDS) with an IPSS score > 2.5, Non-Hodgkin's lymphoma (NHL), Hodgkin's lymphoma (HD) or multiple myeloma, for which all potentially curative or standard salvage therapy options have been exhausted. ECOG performance status < 2. Biochemical values within the following range: Serum creatinine < 2x upper limit of normal. Total bilirubin < 2x upper limit of normal, AST and ALT < 5x upper limit of normal. Normal serum B12 level. Ability to maintain adequate oral intake of medication. Ability to understand and sign informed consent. Toxicity from prior chemotherapy has resolved. Exclusion Criteria: Uncontrolled systemic infection. Uncontrolled intracurrent illness. Pregnant or breast feeding. CNS disease. Neurologic symptoms related to intracurrent illnesses or unexplained causes. Psychiatric illness that would limit compliance with study. Receiving other systemic chemotherapy, other than hydroxyurea to control circulating blast counts, within 10 days of study entry. Hydroxyurea is permitted, however the dose must be stable and unchanged in the 7 days prior to initiation with Clioquinol. Prior therapy with Clioquinol. Use of other investigational antileukemic therapy within two weeks of study entry. Given the neurological side of Clioquinol in the Japanese population, this population, this trial will exclude patients who have a parent of Oriental or Japanese origin or who self-identify as Oriental or Japanese (Appendix 9.2). Active ocular problems including visual migraines and glaucoma. Use of oral or intravenous heavy metal supplements including copper, zinc, and nickel.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Minden, MD
Organizational Affiliation
Princess Margaret Hospital, Canada
Official's Role
Principal Investigator
Facility Information:
Facility Name
Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada

12. IPD Sharing Statement

Learn more about this trial

Study Evaluating the Tolerance and Biological Activity of Oral Clioquinol in Patients With Relapsed or Refractory Hematological Malignancy

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