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

Purpose

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	Intervention	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 Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: 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

Resource links provided by NLM:

Genetics Home Reference related topics: core binding factor acute myeloid leukemia cytogenetically normal acute myeloid leukemia familial acute myeloid leukemia with mutated CEBPA

MedlinePlus related topics: Cancer Chronic Lymphocytic Leukemia Chronic Myeloid Leukemia Leukemia

Drug Information available for: Ciclopirox Ciclopirox olamine

Genetic and Rare Diseases Information Center resources: Chronic Lymphocytic Leukemia Leukemia, B-cell, Chronic Acute Lymphoblastic Leukemia Myelodysplastic Syndromes Myeloid Leukemia Acute Myeloid Leukemia Acute Non Lymphoblastic Leukemia Chronic Myeloid Leukemia Hodgkin Lymphoma Lymphosarcoma Chronic Myeloproliferative Disorders

U.S. FDA Resources

Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:

To evaluate the dose-limiting toxicity, maximum tolerated dose, and recommended phase II dose of ciclopirox olamine. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
To evaluate maximum tolerated dose. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
To evaluate recommended phase II dose of ciclopirox olamine. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

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


Enrollment:	20
Study Start Date:	October 2009
Primary Completion Date:	May 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

Arms

Assigned Interventions

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.

Eligibility


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

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:
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%

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00990587

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

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
Study First Received:	October 6, 2009
Last Updated:	June 19, 2015
Health Authority:	Canada: Health Canada

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, Myeloid Leukemia, Myeloid, Acute Leukemia 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

ClinicalTrials.gov processed this record on September 23, 2016