Details

Autor(en) / Beteiligte

• LeMaistre, C.F.
• Meneghetti, C.
• Rosenblum, M.
• Reuben, J.
• Parker, K.
• Shaw, J.
• Deisseroth, A.
• Woodworth, T.
• Parkinson, D.R.

Titel

Phase I Trial of an Interleukin-2 (IL-2) Fusion Toxin (DAB486IL-2) in Hematologic Malignancies Expressing the IL-2 Receptor

Ist Teil von

• Blood, 1992-05, Vol.79 (10), p.2547-2554

Ort / Verlag

Washington, DC: Elsevier Inc

Erscheinungsjahr

1992

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• DAB486IL-2 is a recombinant fusion toxin in which the native receptor binding domain of diphtheria toxin has been replaced with human interleukin-2 (IL-2). It selectively binds and intoxicates only cells that bear the high-affinity receptor for IL-2. In the first clinical trial of a genetically engineered ligand fusion-toxin, we have treated 18 patients with chemo-therapy-resistant IL-2 receptor expressing hematologic malignancies with escalating doses of DAB486IL-2. The maximal tolerated dose of a daily intravenous bolus of DAB486IL-2 was 0.1 mg/kg per day for 10 doses, established by asymptomatic, reversible elevations of hepatic transaminases without changes in other tests of liver function. Other mild reversible side effects noted were rash, nausea, elevated creatinine, chest tightness, and fever. Pharmacokinetic analysis showed a monophasic clearance of 5.8 ± 0.7 minutes with peak levels of 3,549 ± 1,041 mg/mL at the 0.1 mg/kg dose. Approximately 50% of patients developed an antibody response to diphtheria toxin or DAB486IL-2. The presence of such antibodies did not preclude patients from experiencing an antitumor response as four of the six patients with antitumor effect had detectable antibody titers. Although this was a phase I trial designed to define the safety of DAB486IL-2, remissions were observed in three patients lasting from 5 to over 18 months. The ability to achieve significant tumor reductions in this group of heavily treated patients is encouraging and suggests additional trials are warranted in hematologic malignancies. © 1992 by The American Society of Hematology