Phase I trial of an anti-CD19 deglycosylated ricin a chain immunotoxin in non-hodgkin's lymphoma effect of an intensive schedule of administration
Document Type
Article
Department
Haematology and Oncology, East Africa
Abstract
In a phase I trial, eight patients with non-Hodgkin's B-cell lym-phoma 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 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.
Publication (Name of Journal)
Journal of Immunotherapy
Recommended Citation
Robert, C.,
Michael, K.,
Saleh, M.,
Victor, G.,
Ellen, V.,
Tiepu, L.,
Albert, L.
(1995). Phase I trial of an anti-CD19 deglycosylated ricin a chain immunotoxin in non-hodgkin's lymphoma effect of an intensive schedule of administration. Journal of Immunotherapy, 18(4), 231-241.
Available at:
https://ecommons.aku.edu/eastafrica_fhs_mc_haematol_oncol/121
Comments
This work was published before the author joined Aga Khan University.