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

Condition(s) targeted: Hematologic Malignancy; Acute Lymphocytic Leukemia; Chronic Lymphocytic Leukemia; Myelodysplasia; Acute Myeloid Leukemia; Chronic Myelogenous Leukemia; Hodgkin's Disease

Intervention: Ciclopirox Olamine (Drug)

Phase: Phase 1

Status: Recruiting

Sponsored by: University Health Network, Toronto

Official(s) and/or principal investigator(s):
Mark Minden, MD, Principal Investigator, Affiliation: Princess Margaret Hospital, Canada

Overall contact:
Skeeta Sobrian-Couroux, RN, Phone: 416-946-4501, Ext: 4155, Email: Skeeta.Sobrian-Couroux@uhn.on.ca

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.

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

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

Primary outcome:

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:

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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 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 and ALT < 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 intracurrent illness

3. Pregnant or breast feeding

4. Active CNS 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%

Skeeta Sobrian-Couroux, RN, Phone: 416-946-4501, Ext: 4155, Email: Skeeta.Sobrian-Couroux@uhn.on.ca

Vancouver General Hospital, Vancouver, British Columbia V5Z 1M9, Canada; Recruiting
Donna Hogge, MD, Phone: (604) 875-4863, Email: dhogge@bccancer.bc.ca
Donna Hogge, MD, Principal Investigator

Princess Margaret Hospital, Toronto, Ontario M5G 2M9, Canada; Recruiting
Skeeta Sobrian-Couroux, RN, Phone: 416-946-4501, Ext: 4155, Email: Skeeta.Sobrian-Couroux@uhn.on.ca
Mark Minden, MD, Principal Investigator

Starting date: October 2009
Last updated: September 22, 2011