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

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00990587
• Other study ID #: CPX V001
• Status: Completed
• Phase: Phase 1
• First received: October 6, 2009
• Last updated: June 19, 2015
• Start date: October 2009

Study information

• Verified date: June 2015
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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%

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Lymphocytic Leukemia
• Acute Myeloid Leukemia
• Chronic Lymphocytic Leukemia
• Chronic Myelogenous Leukemia
• Hematologic Malignancy
• Hodgkin Disease
• Hodgkin's Disease
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplasia
• Myelodysplastic Syndromes
• Neoplasms
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia

Intervention

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.

Locations

Country	Name	City	State
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia

Sponsors (2)

Lead Sponsor	Collaborator
University Health Network, Toronto	The Leukemia and Lymphoma Society

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the dose-limiting toxicity, maximum tolerated dose, and recommended phase II dose of ciclopirox olamine.		2 years	Yes
Primary	To evaluate maximum tolerated dose.		2 years	Yes
Primary	To evaluate recommended phase II dose of ciclopirox olamine.		2 years	Yes
Secondary	To determine the pharmacodynamic effects of ciclopirox olamine on survivin expression, and relate to the steady-state plasma concentrations of ciclopirox olamine.		2 years	Yes
Secondary	To determine the response rate of ciclopirox olamine.		2 years	Yes
Secondary	To characterize the pharmacokinetics (PK) of ciclopirox olamine in patients with relapsed or refractory hematologic malignancy.		2 years	Yes