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

Study Overview
=================
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.

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

Conditions
-----------------
Hematologic Malignancy, Acute Lymphocytic Leukemia, Chronic Lymphocytic Leukemia, Myelodysplasia, Acute Myeloid Leukemia, Chronic Myelogenous Leukemia, Hodgkin's Disease

Intervention / Treatment
-----------------
* Drug: Ciclopirox Olamine


Participation Criteria
=================
Eligibility 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: Serum creatinine < 2x upper limit of normal. 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%

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ciclopirox Olamine<br>Patients will take Ciclopirox Olamine at escalating doses depending on when they enter into the trial. | Drug: Ciclopirox Olamine<br>* 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the dose-limiting toxicity, maximum tolerated dose, and recommended phase II dose of ciclopirox olamine. |  | 2 years | 
| To evaluate maximum tolerated dose. |  | 2 years | 
| To evaluate recommended phase II dose of ciclopirox olamine. |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the pharmacodynamic effects of ciclopirox olamine on survivin expression, and relate to the steady-state plasma concentrations of ciclopirox olamine. |  | 2 years | 
| To determine the response rate of ciclopirox olamine. |  | 2 years | 
| To characterize the pharmacokinetics (PK) of ciclopirox olamine in patients with relapsed or refractory hematologic malignancy. |  | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
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)