Document Detail

Fludarabine plus alemtuzumab versus fludarabine alone in patients with previously treated chronic lymphocytic leukaemia: a randomised phase 3 trial.
MedLine Citation:
PMID:  21992852     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Chronic lymphocytic leukaemia (CLL) is an incurable and chronic disorder, with worsening prognosis for patients as their disease progresses. We compared the efficacy and safety of the combination of fludarabine and alemtuzumab with fludarabine monotherapy in previously treated patients with relapsed or refractory CLL.
METHODS: Patients (aged ≥ 18 years) with CLL Binet stage A, B, or C or Rai stages I-IV were randomly assigned in a 1:1 ratio according to a computer-generated allocation schedule to open-label combination treatment (fludarabine 30 mg/m(2) per day and alemtuzumab 30 mg per day on days 1-3) or monotherapy (fludarabine 25 mg/m(2) on days 1-5) by use of an interactive voice response system. Both regimens were given intravenously for a maximum of six 28-day cycles. The primary endpoint was progression-free survival (PFS). Analysis was by intention to treat. This trial is registered with, number NCT00086580.
FINDINGS: Fludarabine plus alemtuzumab (n=168) resulted in better PFS than did fludarabine monotherapy (n=167; median 23·7 months [95% CI 19·2-28·4] vs 16·5 months [12·5-21·2]; hazard ratio 0·61 [95% CI 0·47-0·80]; p=0·0003) and overall survival (median not reached vs 52·9 months [40·9-not reached]; 0·65 [0·45-0·94]; p=0·021) compared with fludarabine alone. All-cause adverse events occurred in 161 (98%) of 164 patients in the combination treatment group and 149 (90%) of 165 in the fludarabine alone group. Patients in the fludarabine plus alemtuzumab group had more cytomegalovirus events (23 [14%] vs one [<1%]) and grade 1 or 2 potentially alemtuzumab infusion-related adverse reactions (102 [62%] vs 22 [13%]). Grade 3 or 4 toxicities in the combination treatment and monotherapy groups were leucopenia (121 [74%] of 164 vs 55 [34%] of 164), lymphopenia (149 [94%] of 158 vs 53 [33%] of 161), neutropenia (93 [59%] of 157 vs 110 [68%] of 161), thrombocytopenia (18 [11%] of 164 vs 27 [17%] of 163), and anaemia (14 [9%] of 163 vs 28 [17%] of 164). The incidence of serious adverse events was higher in the combination treatment group (54 [33%] of 164 vs 41 [25%] of 165); deaths due to adverse events were similar between the two groups (ten [6%] vs 12 [7%]).
INTERPRETATION: The combination of fludarabine and alemtuzumab is another treatment option for patients with previously treated CLL.
FUNDING: Genzyme.
Thomas Elter; Liana Gercheva-Kyuchukova; Halyna Pylylpenko; Tadesuz Robak; Branimir Jaksic; Grigoriy Rekhtman; Sławomira Kyrcz-Krzemień; Mykola Vatutin; Jingyang Wu; Cynthia Sirard; Michael Hallek; Andreas Engert
Publication Detail:
Type:  Clinical Trial, Phase III; Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2011-10-10
Journal Detail:
Title:  The Lancet. Oncology     Volume:  12     ISSN:  1474-5488     ISO Abbreviation:  Lancet Oncol.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-11-29     Completed Date:  2012-01-18     Revised Date:  2014-08-18    
Medline Journal Info:
Nlm Unique ID:  100957246     Medline TA:  Lancet Oncol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1204-13     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
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MeSH Terms
Antibodies, Monoclonal, Humanized / administration & dosage
Antibodies, Neoplasm / administration & dosage
Antineoplastic Combined Chemotherapy Protocols / adverse effects,  therapeutic use*
Disease-Free Survival
Kaplan-Meier Estimate
Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*,  mortality,  pathology
Middle Aged
Neoplasm Staging
North America
Proportional Hazards Models
Risk Assessment
Risk Factors
Time Factors
Treatment Outcome
Vidarabine / administration & dosage,  analogs & derivatives
Reg. No./Substance:
0/Antibodies, Monoclonal, Humanized; 0/Antibodies, Neoplasm; 3A189DH42V/alemtuzumab; FA2DM6879K/Vidarabine; P2K93U8740/fludarabine

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