A randomized placebo-controlled clinical trial of the anti-angiogenic thromobspondin-mimetic peptide ABT-526 plus Lomustine chemotherapy versus Lomustine chemotherapy alone in pet dogs with relapsed non-Hodgkin’s lymphoma.
Background:
Thrombospondin-1 (TSP-1) is a natural antiangiogenic protein that enhances apoptosis of activated endothelial cells (EC). A modified nonapeptide from thrombospondin-1, ABT-526, has been found to be active in mouse cancer models and in dogs with naturally occurring cancers.
Methods:
To assess the safety and efficacy of ABT-526 when given in combination with Lomustine chemotherapy, 94 pet dogs with naturally occurring non-Hodgkin’s lymphoma (NHL), in their first relapse, were entered to a prospective randomized placebo controlled double-blinded clinical trial. Dogs were randomly assigned to receive ABT-526 plus Lomustine versus placebo plus Lomustine. Response rate, duration of response, time to progression, and incidence of toxicoses were compared between groups.
Results:
No significant ABT-526 specific toxicities were seen. Lomustine associated dose-limiting toxicities, including neutropenia, thrombocytopenia, gastroenteritis, and elevated alanine transaminase, were similar between treatment groups. No significant difference in the objective response rate was seen between treatment groups [ABT-526+Lomustine = 23/49 (47%) vs placebo+Lomustine = 23/37 (62%); P>0.25]. However, the median response duration was significantly greater in patients receiving ABT-526 plus Lomustine compared to placebo plus Lomustine (35 days vs 15 days; P=0.05). The time to progression for responding cases was also significantly greater in patients receiving ABT-526 plus Lomustine compared to placebo plus Lomustine (41 days vs 21 days; P=0.047).
Conclusions:
The significant activity of ABT-526 demonstrated in this preclinical trial appears to be associated with the maintenance of Lomustine induced treatment responses. Further studies of ABT-526, in this relevant naturally occurring model of NHL, are warranted and may be used to define biomarkers that predict responsiveness to antiangiogenic therapy and evaluate the activity of ABT-526 in combination with conventional and novel treatment agents.
Pet owners seeking novel treatment options for animals with serious health conditions find an Animal Clinical Investigation network veterinarian participating in a clinical trial.
Animal Clinical Investigation network veterinarian and pet owner work together to determine whether the pet is eligible for the trial. Eligible pets begin treatment at an ACI network hospital.
Information from the trial is used to help develop new drugs and treatments, providing a source of hope for people whose pets face serious illnesses.