Phase I study of the anti-CD74 monoclonal antibody milatuzumab (hLL1) in patients with previously treated B-cell lymphomas.

Abstract	Milatuzumab (hLL1), a humanized anti-CD74 monoclonal antibody, has activity in preclinical non-Hodgkin lymphoma (NHL) models. We conducted a phase 1 trial in previously treated B-cell malignancies. Dose escalation included four planned dose levels (1.5, 4, 6 and 8 mg/kg) with milatuzumab given twice weekly for 6 weeks. After dose level 1, the schedule was changed to daily (Monday-Friday) for 10 days. Twenty-two patients were treated. The most common possibly related toxicities were infusion reaction, anemia, lymphopenia, neutropenia and thrombocytopenia. Three patients experienced dose-limiting toxicity (neutropenia, neutropenia, rash) at dose levels 1, 2 and 4, respectively. Eight patients had stable disease, with no objective responses. The serum half-life of milatuzumab was ∼2 h. In seven patients, In-111 imaging showed no clear evidence of tumor targeting. The short half-life may reflect CD74 rapid internalization and presence on extratumoral tissues; this antigen sink must be overcome to capitalize on the promising preclinical activity of the drug.
Authors	Peter Martin, Richard R Furman, Sarah Rutherford, Jia Ruan, Scott Ely, June Greenberg, Morton Coleman, Stanley J Goldsmith, John P Leonard
Journal	Leukemia & lymphoma (Leuk Lymphoma) Vol. 56 Issue 11 Pg. 3065-70 ( 2015) ISSN: 1029-2403 [Electronic] United States
PMID	25754579 (Publication Type: Clinical Trial, Phase I, Journal Article)
Chemical References	Antibodies, Monoclonal, Humanized Antigens, Differentiation, B-Lymphocyte Antineoplastic Agents Biomarkers Histocompatibility Antigens Class II invariant chain milatuzumab
Topics	Adult Aged Antibodies, Monoclonal, Humanized (pharmacology, therapeutic use) Antigens, Differentiation, B-Lymphocyte (metabolism) Antineoplastic Agents (pharmacology, therapeutic use) Biomarkers Disease Progression Drug Resistance, Neoplasm Female Histocompatibility Antigens Class II (metabolism) Humans Immunohistochemistry Lymphoma, B-Cell (diagnosis, drug therapy) Male Middle Aged Neoplasm Staging Recurrence Retreatment Tissue Distribution Treatment Outcome

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