title: Alemtuzumab consolidation in chronic lymphocytic leukaemia: a phase I/II multicentre trial.
abstract: OBJECTIVE
  Despite high rates of long-lasting remissions in patients with chronic lymphocytic leukaemia (CLL) treated with chemoimmunotherapy, none of the current therapeutic approaches is curative with the exception of allogeneic transplantation. One strategy to extend progression-free survival and long-term survival might be the establishment of consolidation therapies.
  
  
  METHODS
  In this trial, patients with complete or partial second remission after fludarabine-based treatment received consolidation therapy with alemtuzumab. The aim of this phase I/II trial was to determine the maximal tolerable dose (MTD) of alemtuzumab consolidation and to evaluate safety and efficacy in patients who responded to second-line fludarabine-based treatment. Thirteen patients in complete (CR) or partial remission (PR) received alemtuzumab dose escalation starting with 10 mg intravenously (iv) once weekly for 8 wk and increasing in 10-mg intervals per dose level.
  
  
  RESULTS
  The main dose-limiting toxicities (DLTs) were infectious complications, and the MTD was determined at 10 mg. After alemtuzumab consolidation, seven of 13 patients (53%) were in CR, and four of these patients (30.7%) achieved minimal residual disease (MRD) negativity (<1 × 10E-4). At a median follow-up of 71.5 months, four patients were progression-free, with a median progression-free survival (PFS) of 28.5 months after the end of second-line treatment.
  
  
  CONCLUSIONS
  The results provide a safe and efficient schedule with weekly intravenous application of 10 mg of alemtuzumab as a consolidation regime in patients with CLL.
authors.affiliation: Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, German CLL Study group, University of Cologne, Cologne, Germany.
authors.forename: Othman
authors.initials: O
authors.lastname: Al-Sawaf
authors.affiliation: Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, German CLL Study group, University of Cologne, Cologne, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Fischer
authors.affiliation: Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, German CLL Study group, University of Cologne, Cologne, Germany.
authors.forename: Carmen D
authors.initials: CD
authors.lastname: Herling
authors.affiliation: Department II of Internal Medicine, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Ritgen
authors.affiliation: Department II of Internal Medicine, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Böttcher
authors.affiliation: Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, German CLL Study group, University of Cologne, Cologne, Germany.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Bahlo
authors.affiliation: Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, German CLL Study group, University of Cologne, Cologne, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Elter
authors.affiliation: Department III of Internal Medicine, University Hospital Ulm, Ulm, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Stilgenbauer
authors.affiliation: Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, German CLL Study group, University of Cologne, Cologne, Germany.
authors.forename: Barbara F
authors.initials: BF
authors.lastname: Eichhorst
authors.affiliation: Institute for Medical Statistic and Epidemiology, Technical University, Munich, Germany.
authors.forename: Raymonde
authors.initials: R
authors.lastname: Busch
authors.affiliation: Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, German CLL Study group, University of Cologne, Cologne, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Elberskirch
authors.affiliation: MOP Elisenhof, Munich, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Abenhardt
authors.affiliation: Department II of Internal Medicine, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Kneba
authors.affiliation: Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, German CLL Study group, University of Cologne, Cologne, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hallek
authors.affiliation: Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, German CLL Study group, University of Cologne, Cologne, Germany.|Department of Hematology, Oncology, Immunology, Palliative Care, Infectious Diseases and Tropical Medicine, Klinikum Schwabing, Munich, Germany.
authors.forename: Clemens-Martin
authors.initials: CM
authors.lastname: Wendtner
mesh_terms: D000368:Aged; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D060830:Consolidation Chemotherapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018365:Neoplasm, Residual / Q000175:diagnosis; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000074323:Alemtuzumab
keywords: alemtuzumab; chronic lymphocytic leukaemia; consolidation