title: A phase I study of escalated dose subcutaneous alemtuzumab given weekly with rituximab in relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma.
abstract: This study assessed the safety and preliminary efficacy of escalated dose subcutaneous alemtuzumab in combination with rituximab in chronic lymphocytic leukemia. Twenty-eight patients with relapsed refractory chronic lymphocytic leukemia were treated on four dosing cohorts of weekly rituximab at 375 mg/m(2) and alemtuzumab doses that started at 30 mg three times per week and escalated to weekly dosing over four weeks, culminating with 90 mg weekly. One dose limiting toxicity of a rituximab infusion reaction was seen in cohort 2, but the regimen was otherwise well tolerated without evidence of differential toxicity by cohort. The overall response rate by National Cancer Institute-Working Group criteria was 61%, and the rate of complete bone marrow response was 43%, most of whom were negative for minimal residual disease. The addition of CT scan evaluation per International Workshop on Chronic Lymphocytic Leukemia 2008 criteria reduced the overall response rate to 14%. Median overall survival was 35 months, with 12 patients able to proceed to stem cell transplantation. Pharmacokinetic studies showed that chronic lymphocytic leukemia involving more than 80% of the bone marrow at study start was associated with lower trough concentrations of alemtuzumab and rituximab, and that higher trough serum concentrations of alemtuzumab were associated with complete bone marrow clearance. We conclude that escalated subcutaneous doses of alemtuzumab given weekly are well tolerated and result in excellent bone marrow clearance of chronic lymphocytic leukemia, helping patients to proceed to stem cell transplantation. This study is registered at ClinicalTrials.gov (Identifier:00330252).
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. jbrown2@partners.org
authors: Jennifer R
authors: JR
authors: Brown
authors: Bradley
authors: B
authors: Messmer
authors: Lillian
authors: L
authors: Werner
authors: Matthew S
authors: MS
authors: Davids
authors: Evgeny
authors: E
authors: Mikler
authors: Jeffrey G
authors: JG
authors: Supko
authors: David C
authors: DC
authors: Fisher
authors: Ann S
authors: AS
authors: LaCasce
authors: Philippe
authors: P
authors: Armand
authors: Eric
authors: E
authors: Jacobsen
authors: Virginia
authors: V
authors: Dalton
authors: Bethany
authors: B
authors: Tesar
authors: Stacey M
authors: SM
authors: Fernandes
authors: Sean
authors: S
authors: McDonough
authors: Jerome
authors: J
authors: Ritz
authors: Laura
authors: L
authors: Rassenti
authors: Thomas J
authors: TJ
authors: Kipps
authors: Donna
authors: D
authors: Neuberg
authors: Arnold S
authors: AS
authors: Freedman
mesh_terms: D000368:Aged; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000493:pharmacokinetics; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012008:Recurrence; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000074323:Alemtuzumab; D000069283:Rituximab
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