A multi-center pivotal field study to confirm the effectiveness and safety of verdinexor for the treatment of lymphoma in dogs

Standard treatment of lymphoma involves a 16-week conventional chemotherapy protocol with an 80% response rate for an average of 10 to 12 months. This study is an investigation to evaluate the safety and effectiveness of a new treatment (verdinexor) for lymphoma in dogs.

This pivotal field study (clinical trial) is a randomized, masked, placebo-controlled, pivotal effectiveness study. The study will test the investigational drug compared to a placebo (a tablet that does not contain the investigational drug). There is a 1 in 5 chance that your dog will receive the placebo tablets. Because this drug is conditionally licensed and commercially available you can elect to purchase this drug at your own cost; your pet would not be enrolled in the study, but it would ensure that your pet would not receive a placebo treatment.

Inclusion Criteria

For a dog to be eligible for study enrollment, all of the following inclusion criteria must be met:

• Written informed owner consent has been obtained prior to screening
• Dog is older than 1 year
• Dog weighs 9 kg or more (note: this weight limitation is based on the ability to accurately dose a dog weighing less than 9 kg and available safety information)
• Dog has naïve or first relapse lymphoma:
  • Naïve: dog who has not received any treatment for lymphoma
  • First relapse: dog has failed a single round of any chemotherapy completed at least 14-days prior to study entry and has recovered from any acute toxicity from prior chemotherapy, or is on prednisone and has exhibited progressive disease
• Evidence of disease (progression) at the time of screening is based on direct measurement of at least one peripheral lymph node > 20 mm longest diameter(LD)
• Dog has histological or cytological diagnosis of B-cell or T-cell lymphoma (confirmed by flow cytometry prior to or during screening procedures), stages II, III, or IV:
  • Stage II: Regional lymphadenopathy (restricted to one side of diaphragm)
  • Stage III: Generalized lymphadenopathy (enlargement of lymph nodes)
  • Stage IV: Hepatosplenomegaly (provided there is also lymphadenopathy such that the Investigator can assess disease status through a physical exam)
• A modified Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1 [0 = normal activity, 1 = restricted activity, decreased from pre-disease status]
• Dog has a life expectancy of at least 28 days
• If on NSAIDs treatment, the dog has been treated for more than 2 weeks prior to enrollment

Exclusion Criteria

If present, the following exclusion criteria will disqualify a dog from being enrolled in the study:

• Dog has stage I lymphoma
• Dog has clinical evidence of stage V lymphoma involving the CNS, gastrointestinal tract or pulmonary system
• Dogs that have a lymphocyte count greater than 15,000 per µL
• Dog has received prior radiation specifically for the treatment of lymphoma
• Dog has a clinically relevant abnormal laboratory result that in the opinion of the Investigator may interfere with the outcome of the study
• Dog has a serious, concurrent medical condition (e.g., renal, cardiovascular, hepatic, endocrine, concurrent malignancy) that may preclude a successful lymphoma treatment outcome
• Dog has significant bulky disease such that clinical deterioration is likely to occur even in the setting of stable disease
• Dog is participating in another study or is receiving an investigational Therapy
• Dog has received any immunotherapy for the treatment of lymphoma
• Dog is receiving complementary or alternative medicines that the Investigator believes could interfere with the primary endpoint of the study
• Dog that is lactating, pregnant, or intended for breeding

Client Benefits

If you elect to enroll your dog in the study, the study sponsor will provide the investigational treatment for lymphoma to be used during the study and pay for the cost of the examinations and tests. Your dog will be evaluated weekly and if there is evidence of progression of lymphoma (meaning the lymph nodes are enlarging in size) your dog will complete the study and if on placebo you will be offered the study drug if you elect. If your pet is on the study drug (not placebo) and their lymphoma progresses, you can pursue additional chemotherapy treatments if you elect. Additional chemotherapy treatments are not covered by the study.

If your dog has any adverse events that are study-related and require treatment, the sponsor will cover the costs of reasonable treatment. If your dog is withdrawn due to other factors, your veterinarian will be compensated for the portion of the study your dog did complete.

Sample or Data Requirements

Your participation in the study will be for 56 days during which time you will need to bring your dog to the veterinary clinic for scheduled or unscheduled follow-up visits. There will be a minimum of once-weekly visits to the clinic for up to 6 weeks. You will need to administer the study medication to your pet twice weekly and record the dose in a form that will be sent home with you. You will also record any abnormal health issues occurring in your pet in an additional form.