Phase I trial of an anti-CD19 deglycosylated ricin A chain immunotoxin in non-Hodgkin's lymphoma

Effect of an intensive schedule of administration

R. M. Conry, M. B. Khazaeli, M. N. Saleh, V. Ghetie, E. S. Vitetta, T. Liu, A. F. LoBuglio

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

In a phase I trial, eight patients with non-Hodgkin's B-cell lymphoma received mouse IgGlk 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 μg/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.

Original languageEnglish (US)
Pages (from-to)231-241
Number of pages11
JournalJournal of Immunotherapy
Volume18
Issue number4
StatePublished - 1995

Fingerprint

Ricin
Immunotoxins
Non-Hodgkin's Lymphoma
Appointments and Schedules
Capillary Leak Syndrome
Serum
Bronchopneumonia
Hypoalbuminemia
Orthostatic Hypotension
Rhabdomyolysis
Maximum Tolerated Dose
B-Cell Lymphoma
Weight Gain
Antibody Formation
Half-Life
Anti-Idiotypic Antibodies
Monoclonal Antibodies
Antibodies

Keywords

  • Immunotherapy
  • Immunotoxin
  • Monoclonal antibody
  • Non-Hodgkin's lymphoma
  • Ricin A chain

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

Cite this

Phase I trial of an anti-CD19 deglycosylated ricin A chain immunotoxin in non-Hodgkin's lymphoma : Effect of an intensive schedule of administration. / Conry, R. M.; Khazaeli, M. B.; Saleh, M. N.; Ghetie, V.; Vitetta, E. S.; Liu, T.; LoBuglio, A. F.

In: Journal of Immunotherapy, Vol. 18, No. 4, 1995, p. 231-241.

Research output: Contribution to journalArticle

Conry, R. M. ; Khazaeli, M. B. ; Saleh, M. N. ; Ghetie, V. ; Vitetta, E. S. ; Liu, T. ; LoBuglio, A. F. / Phase I trial of an anti-CD19 deglycosylated ricin A chain immunotoxin in non-Hodgkin's lymphoma : Effect of an intensive schedule of administration. In: Journal of Immunotherapy. 1995 ; Vol. 18, No. 4. pp. 231-241.
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