Clinical trial NCT00990587: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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)
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: The Leukemia and Lymphoma Society
First posted: 2009-10-07
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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%

Primary outcomes:
measure: To evaluate the dose-limiting toxicity, maximum tolerated dose, and recommended phase II dose of ciclopirox olamine.
timeFrame: 2 years
measure: To evaluate maximum tolerated dose.
timeFrame: 2 years
measure: To evaluate recommended phase II dose of ciclopirox olamine.
timeFrame: 2 years
Secondary outcomes:
measure: To determine the pharmacodynamic effects of ciclopirox olamine on survivin expression, and relate to the steady-state plasma concentrations of ciclopirox olamine.
timeFrame: 2 years
measure: To determine the response rate of ciclopirox olamine.
timeFrame: 2 years
measure: To characterize the pharmacokinetics (PK) of ciclopirox olamine in patients with relapsed or refractory hematologic malignancy.
timeFrame: 2 years
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: Princess Margaret Hospital, Canada
name: Mark Minden, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.