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

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Hematologic Malignancy; Acute Lymphocytic Leukemia; Chronic Lymphocytic Leukemia; Myelodysplasia; Acute Myeloid Leukemia; Chronic Myelogenous Leukemia; Hodgkin's Disease	Drug: Ciclopirox Olamine	Phase 1

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	20 participants
Allocation:	Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Phase 1 Study Evaluating the Tolerance and Biologic Activity of Oral Ciclopirox Olamine in Patients With Relapsed or Refractory Hematologic Malignancy
Study Start Date :	October 2009
Actual Primary Completion Date :	May 2013

Arms and Interventions

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Arm

Intervention/treatment

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

Drug: Ciclopirox Olamine; 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.

Outcome Measures

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Primary Outcome Measures :

1. To evaluate the dose-limiting toxicity, maximum tolerated dose, and recommended phase II dose of ciclopirox olamine. [ Time Frame: 2 years ]
2. To evaluate maximum tolerated dose. [ Time Frame: 2 years ]
3. To evaluate recommended phase II dose of ciclopirox olamine. [ Time Frame: 2 years ]

Secondary Outcome Measures :

1. 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 ]
2. To determine the response rate of ciclopirox olamine. [ Time Frame: 2 years ]
3. To characterize the pharmacokinetics (PK) of ciclopirox olamine in patients with relapsed or refractory hematologic malignancy. [ Time Frame: 2 years ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. Age > 18
2. 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.
3. ECOG (Eastern Cooperative Oncology Group) performance status < 2.

4. 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.
5. Ability to maintain adequate oral intake of medication.
6. Ability to understand and sign informed consent.
7. Toxicity from prior chemotherapy has resolved

Exclusion Criteria:

1. Uncontrolled systemic infection.
2. Uncontrolled intercurrent illness
3. Pregnant or breast feeding
4. Active CNS (central nervous system) 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 ciclopirox olamine
8. Concurrent therapy with topical ciclopirox olamine.
9. Use of other investigational anti-cancer therapy within two weeks of study entry.
10. Use of oral or intravenous metal supplements including iron, copper, zinc and nickel.
11. Resting ejection fraction < 50%

Contacts and Locations

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Locations

Canada, British Columbia
Vancouver General Hospital
Vancouver, British Columbia, Canada, V5Z 1M9
Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9

Sponsors and Collaborators

University Health Network, Toronto

The Leukemia and Lymphoma Society

Investigators

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

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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 β-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.

Responsible Party:	University Health Network, Toronto
ClinicalTrials.gov Identifier:	NCT00990587 History of Changes
Other Study ID Numbers:	CPX V001
First Posted:	October 7, 2009
Last Update Posted:	June 22, 2015
Last Verified:	June 2015

Keywords provided by University Health Network, Toronto:

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)

Additional relevant MeSH terms:

Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Neoplasms; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Hodgkin Disease; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Preleukemia; Neoplasms by Histologic Type; Lymphoproliferative Disorders	Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Lymphoma; Precancerous Conditions; Ciclopirox; Antifungal Agents; Anti-Infective Agents