This study is closed. (11/9/12)

Purpose of Study

The purpose of this study is to evaluate the safety and tolerability of KPT-335 given on a compassionate use basis to dogs with Lymphoma

Background

In both normal and cancerous cells, proteins important in regulating cell growth and survival regularly move between the cell cytoplasm and the nucleus (center) of the cell.  This shuttling of proteins is tightly controlled and helps to decide which genes get turned on and which genes get turned off.  It is known that a specific protein in the membrane of the nucleus, CRM1, controls the shuttling of several key proteins in and out of the nucleus.  In fact, over 150 proteins have been found to use CRM1 to leave the nucleus of the cell and enter the cytoplasm.  In cancer cells, the function of CRM1 is critical to maintaining the uncontrolled growth and survival of these cells.  Recent studies indicate that blocking CRM1 can induce death of cancer cells as they cannot recover function when the shuttling of proteins is disrupted; in contrast, normal cells appear to be less sensitive to this effect, likely because they are not growing in an uncontrolled manner.    The novel compound KPT-335 is an irreversible inhibitor of CRM1; that is, once it binds, CRM1 cannot function unless new CRM1 protein is made.   Studies in the laboratory have shown that KPT-335 kills a variety of cancer cell lines, even those known to be resistant to chemotherapy. KPT-335 has also demonstrated activity in mouse models of cancer when given by injection under the skin or orally.  KPT-335 has also been tested in normal dogs where doses of 3-5 mg/kg were given Monday, Wednesday, Friday (MWF).  Mild vomiting, diarrhea, and appetite loss did occur; this recovered with the addition of canned food to the diet and supportive care.  In doses above 58 mg/kg, elevations in liver values were observed, although they recovered with discontinuation of drug and the use of a lower dose. 

Inclusion criteria

To qualify for enrollment in this study, dogs must:

• Dogs diagnosed with new or relapsed Lymphoma. The patient may have failed standard therapy or there may be no other known effective antineoplastic therapeutic options, or the owner may elect to enter the patient in lieu of standard therapy.
• Dogs must be at least 1 year of age.
• Adequate organ function as indicated by standard laboratory tests
• Dogs must have an estimated life expectancy of at least 28 days.
• Prior chemotherapy or radiation must be completed at least 2 weeks prior
• Owner must be able to orally administer drug according to designated schedule
• No evidence of brain metastasis
• Can not be less than 2 weeks from a major surgical procedure


Study Design

• Patients will be screened for eligibility, if eligible your dog will receive KPT-335 orally on a Monday-Wednesday-Friday. Drug will be administered on an empty stomach by the owner at home at the same time each morning. Patients will need to return on Weeks 1, 2, 3, and 4.  On these days, the patient will need to arrive with in 2 hours of administering medication for blood levels and blood work.
• Dogs who respond to KPT-335 treatment with an objective response (CR or PR) or stable disease (SD) according to predefined criteria may continue to receive cycles of KPT-335 indefinitely, as long as DLT is not observed.  
• Dogs that miss more than 1 dose of a cycle for toxicity may have their dose reduced by 1 level.  Any dog requiring a delay in dosing of more than 48 hours due to drug toxicity will also have its dose reduced by 1 level.  Patients requiring a dose delay of more than 2 weeks for toxicity possibly, probably, or definitely related to protocol-based therapy will be removed from the study.  If a dose is missed or the entire dose is not given, the dose will not be made up.

Client Compensation

Please note there is an initial visit fee that must be covered by the owner. If your pet is eligible and enrolled into the study the sponsor will cover this fee plus cover study associated costs for screening, exam fees, labwork and up to $750 for any adverse events. Owner will also receive $500 applied to their OSU Vet Account, at the completion of the study, to be used for further treatment at OSU. 

Contact Information

Please contact the Clinical Trials Office at the Veterinary Medical Center for more information about this study.