Hematologic Malignancies, Solid Tumors
Conditions
Keywords
omacetaxine, omacetaxine mepesuccinate, pharmacokinetics, hematologic malignancies, advanced solid tumors
Brief summary
The purpose of this study is to determine the pharmacokinetic and safety profiles of omacetaxine and its metabolites in patients with relapsed and/or refractory hematologic malignancies or advanced solid tumors following subcutaneous (sc) administration.
Detailed description
This is a Phase 1, single-center, open-label, nonrandomized study to determine the pharmacokinetics (absorption, distribution, metabolism, and excretion) of omacetaxine and its metabolites following a sc dosage of 1.25 mg/m2 in adult patients with relapsed and/or refractory hematologic malignancies or advanced solid tumors. The study consists of a screening period of up to 28 days, followed by a 7-day pharmacokinetic assessment period (period A) that includes administration of a single radiolabeled dose of omacetaxine, an open-label treatment period of up to six 28-day cycles (period B), and a final assessment to occur approximately 28±7 days after the end of the last treatment cycle. Period B will begin after collection of the 72-hour pharmacokinetic sample during period A.
Interventions
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent is obtained. * The patient is at least 18 years of age at the time of informed consent. * The patient has a histologically or cytologically confirmed diagnosis of any of the following: * Relapsed or refractory leukemia, including Philadelphia chromosome-positive (Ph+), chronic myelogenous leukemia (CML), acute promyelocytic leukemia (APL), acute myelogenous leukemia (AML), or myelodysplastic syndrome (MDS). * Advanced solid tumors (ie, breast, lung, head/neck, colorectal, melanoma, and sarcoma). The malignancy must be considered unresponsive to accepted available therapies. * The patient has an estimated life expectancy of at least 3 months. * The patient has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2. * Other criteria apply.
Exclusion criteria
* The patient has had chemotherapy, radiotherapy, radioimmunotherapy, or immunotherapy within 28 days prior to the first dose of study drug or has not recovered from adverse events due to any agents administered previously. For patients who received therapy with mitomycin C, the interval is 42 days. * The patient is receiving any other treatment for hematologic/nonhematologic malignancy. * The patient has had previous treatment with omacetaxine. * The patient has been treated with any hematopoietic growth factors within 14 days of study entry (patients on chronic erythropoiesis stimulating agents are allowed). * The patient has New York Heart Association (NYHA) Class 3 or 4 heart disease, active ischemia, or any uncontrolled, unstable cardiac condition for which treatment for the condition is indicated but is not controlled despite adequate therapy, including angina pectoris, cardiac arrhythmia, hypertension, or congestive heart failure. * The patient has experienced a myocardial infarction within the previous 12 weeks. * The patient has a solid tumor with symptomatic central nervous system (CNS) metastases. * The patient has an active, uncontrolled systemic infection considered opportunistic, life threatening, or clinically significant at the time of treatment. * Other criteria apply.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Apparent volume of distribution (Vz/F) | 0,15, 30, and 45 minutes and 1, 2, 4, 8, 12, 24, 32, 48, 72, 96,120, 144, and 168 hours post dose | — |
| Maximum observed plasma drug concentrations (Cmax) | 0,15, 30, and 45 minutes and 1, 2, 4, 8, 12, 24, 32, 48, 72, 96,120, 144, and 168 hours post dose | — |
| Time to Reach Maximum Observed Plasma Drug Concentration (Tmax) | 0,15, 30, and 45 minutes and 1, 2, 4, 8, 12, 24, 32, 48, 72, 96,120, 144, and 168 hours post dose | — |
| Area under the plasma concentration by time curve (AUC) from time 0 to infinity (AUC0-∞) | 0,15, 30, and 45 minutes and 1, 2, 4, 8, 12, 24, 32, 48, 72, 96,120, 144, and 168 hours post dose | — |
| Area under the Curve from Time Zero to the Time of the Last Measurable Drug Concentration (AUC0-t) | 0,15, 30, and 45 minutes and 1, 2, 4, 8, 12, 24, 32, 48, 72, 96,120, 144, and 168 hours post dose | AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t) |
| Terminal rate constant (λz) and associated half-life (t½) | 0,15, 30, and 45 minutes and 1, 2, 4, 8, 12, 24, 32, 48, 72, 96,120, 144, and 168 hours post dose | — |
| Percentage extrapolation calculated as (AUC0-∞-AUC0-t)/(AUC0-∞)x100 | 0,15, 30, and 45 minutes and 1, 2, 4, 8, 12, 24, 32, 48, 72, 96,120, 144, and 168 hours post dose | — |
| Apparent plasma clearance (CL/F) | 0,15, 30, and 45 minutes and 1, 2, 4, 8, 12, 24, 32, 48, 72, 96,120, 144, and 168 hours post dose | — |
Secondary
| Measure | Time frame |
|---|---|
| Summary of participants with adverse events | From Day 1 through the end of the follow-up period (28±7 days after 6 month treatment cycle) |
Countries
Netherlands
Outcome results
None listed