title: Obinutuzumab plus fludarabine/cyclophosphamide or bendamustine in the initial therapy of CLL patients: the phase 1b GALTON trial.
abstract: Obinutuzumab is a type 2, glycoengineered, anti-CD20 antibody recently approved with chlorambucil for the initial therapy of chronic lymphocytic leukemia (CLL). In this nonrandomized, parallel-cohort, phase 1b, multicenter study, we explored the safety and preliminary efficacy of obinutuzumab-bendamustine (G-B) or obinutuzumab fludarabine cyclophosphamide (G-FC) for the therapy of previously untreated fit patients with CLL. Patients received up to 6 cycles of G-B (n = 20) or G-FC (n = 21). The primary end point was safety, with infusion-related reactions (88%, grade 3-4 20%) being the most common adverse event and grade 3-4 neutropenia in 55% on G-B and 48% on G-FC. Mean cycles completed were 5.7 for G-B and 5.1 for G-FC, with 2 and 7 early discontinuations, respectively. The objective response rate (ORR) for G-B was 90% (18/20) with 20% complete response (CR) and 25% CR with incomplete marrow recovery (CRi). The ORR for G-FC was 62% (13/21), with 10% CR and 14% CRi, including 4 patients not evaluable. With a median follow-up of 23.5 months in the G-B cohort and 20.7 months in the G-FC cohort, no patient has relapsed or died. We conclude that obinutuzumab with either B or FC shows manageable toxicity and has promising activity. This study was registered at www.clinicaltrials.gov as #NCT01300247.
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA; CLL Research Consortium;
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Brown
authors.affiliation: University of Texas MD Anderson Cancer Center, Houston, TX;
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.affiliation: Clearview Cancer Institute, Huntsville, AL;
authors.forename: C Daniel
authors.initials: CD
authors.lastname: Kingsley
authors.affiliation: University of California, Los Angeles, Los Angeles, CA;
authors.forename: Herbert
authors.initials: H
authors.lastname: Eradat
authors.affiliation: Fred Hutchinson Cancer Research Center and Department of Medicine, University of Washington, Seattle, WA;
authors.forename: John M
authors.initials: JM
authors.lastname: Pagel
authors.affiliation: Genentech, Inc., South San Francisco, CA; and.
authors.forename: James
authors.initials: J
authors.lastname: Lymp
authors.affiliation: Genentech, Inc., South San Francisco, CA; and.
authors.forename: Jamie
authors.initials: J
authors.lastname: Hirata
authors.affiliation: CLL Research Consortium; Moores Cancer Center, University of California San Diego, La Jolla, CA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Kipps
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000069461:Bendamustine Hydrochloride; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009588:Nitrogen Mustard Compounds / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D009588:Nitrogen Mustard Compounds; D003520:Cyclophosphamide; D000069461:Bendamustine Hydrochloride; D014740:Vidarabine; C543332:obinutuzumab; C024352:fludarabine