H65-RTA is an
immunoconjugate that consists of the A chain of
ricin (RTA), a ribosomal-inhibiting
protein, coupled to a murine
monoclonal antibody (H65) directed against the pan-T-cell
antigen CD5. The
CD5 antigen is heterogeneously expressed on
cutaneous T-cell lymphoma tumor cells, but is not expressed on normal cells except lymphocytes. A phase I trial was therefore conducted in which 14 patients with
cutaneous T-cell lymphoma progressive on other
therapies were treated with up to three cycles of
H65-RTA. The maximal tolerated dose (MTD) of
H65-RTA was 0.33 mg/kg/d administered intravenously for 10 days as defined by
dyspnea at rest at higher doses. Other reversible side effects included
myalgia, mild
hypoalbuminemia with
weight gain, pedal
edema,
fatigue,
fevers, and
chills. Six patients received more than one cycle of
H65-RTA without increased side effects compared with the first cycle. Pharmacokinetic analysis showed that peak serum
drug levels were dose-dependent, and ranged from 1.13 to 5.56 micrograms/mL, with a terminal half-life ranging from 1.0 to 2.9 hours. The development of
antibodies against the
immunoconjugate was associated with a lower peak
drug level, but not with enhanced side effects. Partial responses lasting from 3 to 8 months were documented in four patients. Three of the responding patients received more than one cycle of
H65-RTA in the presence of anti-
immunoconjugate antibodies. The results from this phase I trial suggest that
H65-RTA is an active
drug in the treatment of
cutaneous T-cell lymphoma. The
immunoconjugate may be safely administered repeatedly, even in the presence of anti-
immunoconjugate antibodies, with responses noted. Additional studies at the MTD are needed to define the response rate in this disease.