title: Phase I/II trial of multiple dose 131Iodine-MAb LL2 (CD22) in patients with recurrent non-Hodgkin's lymphoma.
abstract: The purpose of this to evaluate in a phase I/II study the efficacy and toxicity of a multi-dose administration of 131I labeled CD22 monoclonal antibody (131I-MAb-LL2) in escalating dose cohorts administered to relapsed non-Hodgkin's lymphoma (NHL) patients. Twenty-one patients with relapsed NHL received one of four dose levels of 131-MAb-LL2 administered in a twice weekly pattern. Starting with dose level 2, the patients also received 20 mg of unlabeled LL2 prior to each radiolabeled dose administered. Previously stored autologous peripheral blood progenitors were reinfused in case of prolonged cytopenias. Patients could repeat the same treatment if they had stable disease or a response to the first therapy at 8 weeks, and had not received their peripheral blood progenitors with the first cycle. Combining all of the dose cohorts, there were 5 complete responses or complete responses (undetermined) and 2 partial responses for a total response rate of 7/21 (33%). There was no dose response effect with responses documented at all dose levels. Expected toxicities were hematopoietic, requiring stem cell re-infusion in 5 patients. Other toxicities included hypothyroidism in 3 patients, and human anti-mouse antibody formation (HAMA) in 4 patients. In conclusion, 131I-MAb-LL2, when administered in a multi-dose fashion with 20 mg unlabeled antibody pre-dosing, resulted in a response rate of 33% in heavily pre-treated NHL patients. Non-hematologic toxicities were mild and few in number. Further evaluation of this treatment is warranted and further dose escalation will be possible.
authors.affiliation: Department of Internal Medicine, Nebraska Medical Center, Omaha 68198-7680, USA. jmvose@unmc.edu
authors.forename: J M
authors.initials: JM
authors.lastname: Vose
authors.forename: D
authors.initials: D
authors.lastname: Colcher
authors.forename: L
authors.initials: L
authors.lastname: Gobar
authors.forename: P J
authors.initials: PJ
authors.lastname: Bierman
authors.forename: S
authors.initials: S
authors.lastname: Augustine
authors.forename: M
authors.initials: M
authors.lastname: Tempero
authors.forename: P
authors.initials: P
authors.lastname: Leichner
authors.forename: J C
authors.initials: JC
authors.lastname: Lynch
authors.forename: D
authors.initials: D
authors.lastname: Goldenberg
authors.forename: J O
authors.initials: JO
authors.lastname: Armitage
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D015815:Cell Adhesion Molecules; D006801:Humans; D007457:Iodine Radioisotopes / Q000008:administration & dosage; D037102:Lectins; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008875:Middle Aged; D012008:Recurrence; D051918:Sialic Acid Binding Ig-like Lectin 2; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C497867:CD22 protein, human; D015815:Cell Adhesion Molecules; D007457:Iodine Radioisotopes; D037102:Lectins; D051918:Sialic Acid Binding Ig-like Lectin 2