title: A phase 1 multidose study of SGN-30 immunotherapy in patients with refractory or recurrent CD30+ hematologic malignancies.
abstract: Phase 1 testing of SGN-30, a chimeric monoclonal antibody for the treatment of CD30(+) malignancies, was conducted in a multicenter study. To explore the safety profile and establish the maximum tolerated dose (MTD), 24 patients with refractory or relapsed Hodgkin lymphoma or CD30(+) non-Hodgkin lymphoma received 6 weekly doses of intravenous SGN-30 at 4 dose levels (2, 4, 8, or 12 mg/kg). Serum concentrations of SGN-30 rose rapidly and were dose dependent. Adverse events were mild, with nausea, fatigue, and fever attributed to study treatment. One episode of hypersensitivity rash was reported. The MTD was not reached. Serious adverse events included herpes zoster (n = 2), influenza, and pneumonia. One patient with cutaneous anaplastic large cell lymphoma (8 mg/kg) achieved a complete response. Six patients, of whom 4 had Hodgkin lymphoma, achieved stable disease with durations ranging from 6 to 16 months. The pharmacokinetic profile of SGN-30 showed a biphasic disposition, and estimated half-lives ranging between 1 to 3 weeks. The 6 weekly infusions of SGN-30 resulted in approximately 2- to 3-fold accumulation in serum exposures consistently across the dose range. These results demonstrate that weekly administration of SGN-30 is safe and has modest clinical activity in patients with CD30(+) tumors. This trial is registered at http://www.ClinicalTrials.gov as no. NCT00051597.
authors: Siteman Cancer Center, Washington University School of Medicine, St Louis, MO 63110, USA. nbartlet@wustl.edu
authors: Nancy L
authors: NL
authors: Bartlett
authors: Anas
authors: A
authors: Younes
authors: Matthew H
authors: MH
authors: Carabasi
authors: Andres
authors: A
authors: Forero
authors: Joseph D
authors: JD
authors: Rosenblatt
authors: John P
authors: JP
authors: Leonard
authors: Steven H
authors: SH
authors: Bernstein
authors: R Gregory
authors: RG
authors: Bociek
authors: Jennie M
authors: JM
authors: Lorenz
authors: Bruce W
authors: BW
authors: Hart
authors: Jeremy
authors: J
authors: Barton
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity*; D015703:Antigens, CD / Q000097:blood; D005260:Female; D019337:Hematologic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects*; D017730:Ki-1 Antigen / Q000097:blood*; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D018579:Patient Selection; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D017730:Ki-1 Antigen; C504717:SGN-30 monoclonal antibody