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

June 19, 2015 updated by: University Health Network, Toronto

Phase 1 Study Evaluating the Tolerance and Biological Activity of Oral Clioquinol in Patients With Relapsed or Refractory Hematological Malignancy

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

11

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Clioquinol
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.
Drug: Clioquinol
Patients will take Clioquniol at escalating doses depending on when they enter into the trial.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Varies

Secondary Outcome Measures

Outcome Measure
Time Frame
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
Varies

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Health Network, Toronto

Investigators

  • Principal Investigator: Mark Minden, MD, Princess Margaret Hospital, Canada

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2009

Primary Completion (Actual)

September 1, 2013

Study Completion (Actual)

September 1, 2013

Study Registration Dates

First Submitted

August 19, 2009

First Submitted That Met QC Criteria

August 20, 2009

First Posted (Estimate)

August 21, 2009

Study Record Updates

Last Update Posted (Estimate)

June 22, 2015

Last Update Submitted That Met QC Criteria

June 19, 2015

Last Verified

June 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ADS1.0

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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