Phase I trial of an anti-CD19 deglycosylated ricin A chain immunotoxin in non-Hodgkin's lymphoma: effect of an intensive schedule of administration

J Immunother Emphasis Tumor Immunol. 1995 Nov;18(4):231-41.

Abstract

In a phase I trial, eight patients with non-Hodgkin's B-cell lymphoma received mouse IgG1k monoclonal antibody HD37 specific for CD19 conjugated to deglycosylated ricin A chain (dgA) administered in four doses at 4-h intervals with total doses ranging from 4-12 mg/m2. This schedule generated serum levels of immunotoxin which were sustained over 36 h. The plasma half-life of HD37-dgA was 17 +/- 4 (SD) h. The HD37-dgA conjugate was stable in vivo as demonstrated by serum levels of HD37-dgA conjugate comparable to those of total HD37 antibody. Peak serum levels attained after the fourth dose ranged from 0.36 to 5.63 micrograms/ml. Two of seven evaluable patients developed modest human anti-immunotoxin antibody responses. Toxicity in patients 1-7 consisted of dose-dependent capillary leak syndrome with hypoalbuminemia, orthostatic hypotension, and weight gain. Patient 8 died on day 8 with severe capillary leak, bronchopneumonia, and rhabdomyolysis. All patients had progressive disease at 4 weeks except patient 8, who exhibited a near-complete remission before his death. This intensive schedule appears to produce inordinate toxicity with a maximal tolerated total dose of 8 mg/m2.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Anti-Idiotypic / biosynthesis
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / therapeutic use*
  • Antigens, CD19 / immunology*
  • Drug Administration Schedule
  • Female
  • Glycosylation
  • Humans
  • Immunotoxins / administration & dosage*
  • Immunotoxins / pharmacokinetics
  • Immunotoxins / therapeutic use*
  • Lymphoma, B-Cell / drug therapy*
  • Male
  • Middle Aged
  • Ricin / administration & dosage
  • Ricin / pharmacokinetics
  • Ricin / therapeutic use*

Substances

  • Antibodies, Anti-Idiotypic
  • Antibodies, Monoclonal
  • Antigens, CD19
  • Immunotoxins
  • Ricin