title: Phase III study of chlorambucil versus fludarabine as initial therapy for Waldenstrom's macroglobulinemia and related disorders.
abstract: The WM1 study is a prospective randomized open-label study that includes patients with previously untreated Waldenstrom's macroglobulinemia (WM), splenic lymphoma with villous lymphocytes (SLVL), and nonimmunoglobulin (Ig) M lymphoplasmacytic lymphoma (LPL) who have an indication for treatment. At registration, patients are categorized as having WM, SLVL, or LPL, and these cohorts are to be analyzed separately. The aim of the study is to compare the efficacy of oral chlorambucil at a dose of 8 mg/m(2) (6 mg/m(2) for those > 75 years of age) for 10 days every 28 days to a maximum of 12 cycles with oral or intravenous (I.V.) fludarabine at a dose of 40 mg/m(2) orally or 25 mg/m(2) I.V. (30 mg/m(2)orally or 20 mg/m(2)I.V. for those > 75 years of age) for 5 days every 28 days to a maximum of 6 cycles. Primary endpoints are response to therapy and duration of response; secondary endpoints are improvement in hematologic parameters, toxicity of therapy, quality of life, and survival. To detect a difference in response rate of patients with WM of 15%, assuming that the overall response rates will be 50% to chlorambucil and 65% to fludarabine, with a power of 80%, requires the sample size of each group to be 183, indicating the need for collaboration among a number of national investigator groups. As of February 2005, accrual to the study stands at 143. Registration, randomization, and data collection are entirely Internet-based (www.waldenstroms.org), and the study is organized by an international collaboration, with a planned interim analysis and an external data monitoring committee.
authors.affiliation: Department of Haematology, Taunton and Somerset Hospital, Taunton TA1 5DA, UK. s.a.johnson@btinternet.com
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Johnson
authors.forename: Roger G
authors.initials: RG
authors.lastname: Owen
authors.forename: David G
authors.initials: DG
authors.lastname: Oscier
authors.forename: Veronique
authors.initials: V
authors.lastname: Leblond
authors.forename: Vincent
authors.initials: V
authors.lastname: Levy
authors.forename: Ulrich
authors.initials: U
authors.lastname: Jaeger
authors.forename: John F
authors.initials: JF
authors.lastname: Seymour
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000627:therapeutic use*; D002699:Chlorambucil / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013160:Splenic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D002699:Chlorambucil; D014740:Vidarabine; C024352:fludarabine