Phase I immunotoxin trial in patients with B-cell lymphoma.
Fifteen patients with refractory B-cell lymphoma were treated in a Phase I dose escalation clinical trial with a highly potent immunotoxin consisting of the Fab' fragment of a monoclonal anti-CD22 antibody (RFB4) coupled to chemically deglycosylated ricin A chain. All patients had low, intermediate, or high grade non-Hodgkin's lymphoma. The immunotoxin was administered i.v. in two to six doses at 48-h intervals. The peak serum concentration and the t1/2 were not dose dependent among patients and averaged 1.3 micrograms/ml and 86 min, respectively. Three patients made antibody against A chain, and a fourth made antibody against both A chain and mouse immunoglobulin. Antibody responses were low (less than or equal to 85 micrograms/ml) in three patients and were not detected until 1 mo after treatment. The maximum tolerated dose of the immunotoxin was 75 mg/m2. Dose-related toxicities included vascular leak syndrome, fever, anorexia, and myalgia. Dose-limiting toxicities included pulmonary edema and/or effusion, expressive aphasia, and rhabdomyolysis (resulting in reversible kidney failure). There was no evidence of liver dysfunction. Partial responses were achieved in 38% of evaluable patients, and in those patients who had greater than 50% CD22+ tumor cells, 50% of the patients achieved a partial response. Clinical responses were not related to tumor grade and were generally transient, lasting between 1 and 4 mo.
Vitetta
E S
ES
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235.
Stone
M
M
Amlot
P
P
Fay
J
J
May
R
R
Till
M
M
Newman
J
J
Clark
P
P
Collins
R
R
Cunningham
D
D
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000917:Antibody Formation / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007128:Immunoglobulin Fragments / Q000627:therapeutic use; D000922:Immunotoxins / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012276:Ricin / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D007128:Immunoglobulin Fragments; D000922:Immunotoxins; D012276:Ricin