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Study Evaluating the Tolerance and Biologic Activity of Oral Ciclopirox Olamine in Patients With Relapsed or Refractory Hematologic Malignancy

Primary Purpose

Hematologic Malignancy, Acute Lymphocytic Leukemia, Chronic Lymphocytic Leukemia

Status

Completed

Phase

Phase 1

Locations

Canada

Study Type

Interventional

Intervention

Ciclopirox Olamine

About this trial

This is an interventional treatment trial for Hematologic Malignancy focused on measuring relapsed and refractory hematologic malignancy, ALL (acute lymphoid leukemia), CLL (chronic lymphoid leukemia), High risk myelodysplasia (MDS) with an IPSS (International Prognostic Scoring System) score >2.5, CML (chronic myelogenous leukemia) 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:

Age > 18
Relapsed or refractory hematologic malignancies including AML, ALL, CLL, high risk myelodysplasia (International Prognostic Score >2.5), CML blast crisis, multiple myeloma, non-Hodgkin's lymphoma, and Hodgkin's lymphoma for which all potentially curative therapy options have been exhausted.
ECOG (Eastern Cooperative Oncology Group) performance status < 2.
Biochemical values within the following range:
1. Serum creatinine < 2x upper limit of normal.
2. Total bilirubin < 2x upper limit of normal, AST (asparatate aminotransferase) and ALT (alanine aminotransferase) < 5x upper limit of normal.
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 intercurrent illness
Pregnant or breast feeding
Active CNS (central nervous system) 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 ciclopirox olamine
Concurrent therapy with topical ciclopirox olamine.
Use of other investigational anti-cancer therapy within two weeks of study entry.
Use of oral or intravenous metal supplements including iron, copper, zinc and nickel.
Resting ejection fraction < 50%

Sites / Locations

Vancouver General Hospital
Princess Margaret Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ciclopirox Olamine

Arm Description

Patients will take Ciclopirox Olamine at escalating doses depending on when they enter into the trial.

Outcomes

Primary Outcome Measures

To evaluate the dose-limiting toxicity, maximum tolerated dose, and recommended phase II dose of ciclopirox olamine.

To evaluate maximum tolerated dose.

To evaluate recommended phase II dose of ciclopirox olamine.

Secondary Outcome Measures

To determine the pharmacodynamic effects of ciclopirox olamine on survivin expression, and relate to the steady-state plasma concentrations of ciclopirox olamine.

To determine the response rate of ciclopirox olamine.

To characterize the pharmacokinetics (PK) of ciclopirox olamine in patients with relapsed or refractory hematologic malignancy.

Full Information

NCT ID

NCT00990587

First Posted

October 6, 2009

Last Updated

June 19, 2015

Sponsor

University Health Network, Toronto

Collaborators

The Leukemia and Lymphoma Society

1. Study Identification

Unique Protocol Identification Number

NCT00990587

Brief Title

Study Evaluating the Tolerance and Biologic Activity of Oral Ciclopirox Olamine in Patients With Relapsed or Refractory Hematologic Malignancy

Official Title

Phase 1 Study Evaluating the Tolerance and Biologic Activity of Oral Ciclopirox Olamine in Patients With Relapsed or Refractory Hematologic Malignancy

Study Type

Interventional

2. Study Status

Record Verification Date

June 2015

Overall Recruitment Status

Completed

Study Start Date

October 2009 (undefined)

Primary Completion Date

May 2013 (Actual)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Health Network, Toronto

Collaborators

The Leukemia and Lymphoma Society

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is an open-label, single arm study. Approximately 3-30 patients will be enrolled. Patients will receive Oral ciclopirox olamine (aqueous suspension), initial starting dose of 5 mg/m2/day administered as a single dose daily for 5 days. Three patients will initially be treated at each dose level in sequential cohorts. Dose escalation will continue for each subsequent cohort based on toxicity and plasma drug concentrations observed during the previous cohort. Dose escalation will continue until establishment of the maximum tolerated dose (MTD) has been met. Patients who have demonstrated response to treatment, up to 6 total cycles of treatment may be administered. If additional cycles are warranted, ciclopirox olamine will be given at the same dose and frequency as the patient initially received.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hematologic Malignancy, Acute Lymphocytic Leukemia, Chronic Lymphocytic Leukemia, Myelodysplasia, Acute Myeloid Leukemia, Chronic Myelogenous Leukemia, Hodgkin's Disease

Keywords

relapsed and refractory hematologic malignancy, ALL (acute lymphoid leukemia), CLL (chronic lymphoid leukemia), High risk myelodysplasia (MDS) with an IPSS (International Prognostic Scoring System) score >2.5, CML (chronic myelogenous leukemia) 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

Randomized

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ciclopirox Olamine

Arm Type

Experimental

Arm Description

Patients will take Ciclopirox Olamine at escalating doses depending on when they enter into the trial.

Intervention Type

Drug

Intervention Name(s)

Ciclopirox Olamine

Intervention Description

Patients will take Ciclopirox Olamine at various doses depending on which dose level they come into the study at. Ciclopirox olamine will be administered orally as an aqueous suspension without food. The starting dose will be 5 mg/m2/day administered as a single dose daily for 5 days (one cycle). Once a MTD has been determined, the new patients that enter into the trial will then take it at that level.

Primary Outcome Measure Information:

Title

To evaluate the dose-limiting toxicity, maximum tolerated dose, and recommended phase II dose of ciclopirox olamine.

Time Frame

2 years

Title

To evaluate maximum tolerated dose.

Time Frame

2 years

Title

To evaluate recommended phase II dose of ciclopirox olamine.

Time Frame

2 years

Secondary Outcome Measure Information:

Title

To determine the pharmacodynamic effects of ciclopirox olamine on survivin expression, and relate to the steady-state plasma concentrations of ciclopirox olamine.

Time Frame

2 years

Title

To determine the response rate of ciclopirox olamine.

Time Frame

2 years

Title

To characterize the pharmacokinetics (PK) of ciclopirox olamine in patients with relapsed or refractory hematologic malignancy.

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age > 18 Relapsed or refractory hematologic malignancies including AML, ALL, CLL, high risk myelodysplasia (International Prognostic Score >2.5), CML blast crisis, multiple myeloma, non-Hodgkin's lymphoma, and Hodgkin's lymphoma for which all potentially curative therapy options have been exhausted. ECOG (Eastern Cooperative Oncology Group) performance status < 2. Biochemical values within the following range: Serum creatinine < 2x upper limit of normal. Total bilirubin < 2x upper limit of normal, AST (asparatate aminotransferase) and ALT (alanine aminotransferase) < 5x upper limit of normal. 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 intercurrent illness Pregnant or breast feeding Active CNS (central nervous system) 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 ciclopirox olamine Concurrent therapy with topical ciclopirox olamine. Use of other investigational anti-cancer therapy within two weeks of study entry. Use of oral or intravenous metal supplements including iron, copper, zinc and nickel. Resting ejection fraction < 50%

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

Vancouver General Hospital

City

Vancouver

State/Province

British Columbia

ZIP/Postal Code

V5Z 1M9

Country

Canada

Facility Name

Princess Margaret Hospital

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G 2M9

Country

Canada

12. IPD Sharing Statement

Citations:

PubMed Identifier

22009536

Citation

Song S, Christova T, Perusini S, Alizadeh S, Bao RY, Miller BW, Hurren R, Jitkova Y, Gronda M, Isaac M, Joseph B, Subramaniam R, Aman A, Chau A, Hogge DE, Weir SJ, Kasper J, Schimmer AD, Al-awar R, Wrana JL, Attisano L. Wnt inhibitor screen reveals iron dependence of beta-catenin signaling in cancers. Cancer Res. 2011 Dec 15;71(24):7628-39. doi: 10.1158/0008-5472.CAN-11-2745. Epub 2011 Oct 18.

Results Reference

derived

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Study Evaluating the Tolerance and Biologic Activity of Oral Ciclopirox Olamine in Patients With Relapsed or Refractory Hematologic Malignancy

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