title: Phase I trial of an anti-CD19 deglycosylated ricin A chain immunotoxin in non-Hodgkin's lymphoma: effect of an intensive schedule of administration.
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.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham 35294-3300, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Conry
authors.forename: M B
authors.initials: MB
authors.lastname: Khazaeli
authors.forename: M N
authors.initials: MN
authors.lastname: Saleh
authors.forename: V
authors.initials: V
authors.lastname: Ghetie
authors.forename: E S
authors.initials: ES
authors.lastname: Vitetta
authors.forename: T
authors.initials: T
authors.lastname: Liu
authors.forename: A F
authors.initials: AF
authors.lastname: LoBuglio
mesh_terms: D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018941:Antigens, CD19 / Q000276:immunology*; D004334:Drug Administration Schedule; D005260:Female; D006031:Glycosylation; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016393:Lymphoma, B-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012276:Ricin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D018941:Antigens, CD19; D000922:Immunotoxins; D012276:Ricin