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Phase I trial of H65-RTA immunoconjugate in patients with cutaneous T- cell
lymphoma
CF LeMaistre, S Rosen, A Frankel, S Kornfeld, E Saria, C Meneghetti, J Drajesk, D Fishwild, P Scannon and V Byers
Department of Hematology, M.D. Anderson Cancer Center, Houston, TX.
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.
Volume 78,
Issue 5,
pp. 1173-1182,
09/01/1991
Copyright © 1991 by The American Society of Hematology
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