Phase 1 trial of a novel anti-CD20 fusion protein in pretargeted radioimmunotherapy for B-cell non-Hodgkin lymphoma.

Abstract

Pretargeted radioimmunotherapy (PRIT) has the potential to increase the dose of radionuclide delivered to tumors while limiting radiation to normal tissues. The purpose of this phase 1 trial is to assess safety of this multistep approach using a novel tetrameric single-chain anti-CD20-streptavidin fusion protein (B9E9FP) as the targeting moiety in patients with B-cell non-Hodgkin lymphoma (NHL), and to characterize its pharmacokinetics and immunogenicity. All patients received B9E9FP (160 mg/m(2) or 320 mg/m(2)); either 48 or 72 hours later, a synthetic clearing agent (sCA) was administered (45 mg/m(2)) to remove circulating unbound B9E9FP. (90)Yttrium ((90)Y; 15 mCi/m(2))/(111)In (5 mCi)-DOTA-biotin was injected 24 hours later. There were 15 patients enrolled in the study. B9E9FP had a mean plasma half-life (T(1/2)) of 25 +/- 6 hours with a reduction in plasma level of more than 95% within 6 hours of sCA administration. (90)Y/(111)In-DOTA-biotin infusion resulted in rapid tumor localization and urinary excretion. The ratio of average tumor to whole-body radiation dose was 49:1. No significant hematologic toxicities were noted in 12 patients. There were 2 patients who had hematologic toxicity related to progressive disease. There were 2 complete remissions (90 and 325 days) and one partial response (297 days). B9E9FP performs well as the targeting component of PRIT with encouraging dosimetry, safety, and efficacy. A dose escalation trial of (90)Y-DOTA-biotin in this format is warranted.

• Authors: Andres Forero, Paul L Weiden, Julie M Vose, Susan J Knox, Albert F LoBuglio, Jordan Hankins, Michael L Goris, Vincent J Picozzi, Don B Axworthy, Hazel B Breitz, Robert B Sims, Richard G Ghalie, Sui Shen, Ruby F Meredith
• Journal: Blood (Blood) Vol. 104 Issue 1 Pg. 227-36 (Jul 01 2004) ISSN: 0006-4971 [Print] United States
• PMID: 14996706 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens, CD20
• Recombinant Fusion Proteins

Topics

• Adult
• Aged
• Aged, 80 and over
• Antigens, CD20 (immunology)
• Cohort Studies
• Female
• Gamma Cameras
• Humans
• Lymphoma, B-Cell (diagnostic imaging, immunology, metabolism, radiotherapy)
• Male
• Middle Aged
• Pilot Projects
• Radioimmunotherapy (adverse effects, methods)
• Radionuclide Imaging
• Recombinant Fusion Proteins (administration & dosage, adverse effects, immunology, pharmacokinetics)
• Tissue Distribution