Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial

  title={Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial},
  author={Michael Hallek and Kirsten Fischer and G{\"u}nter Fingerle-Rowson and A.-M. Fink and Raimonde Busch and Jiř{\'i} Mayer and Manfred Hensel and Georg Hopfinger and Georg Hess and Ulrich von Gr{\"u}nhagen and Manuela A Bergmann and John Vincent Catalano and P. L. Zinzani and Federico caligaris-Cappio and J F Seymour and Alan Berrebi and Ulrich J{\"a}ger and Bruno Cazin and Marek Trněn{\'y} and Anne Westermann and Cm Wendtner and B. Eichhorst and Peter Anton Staib and Andreas B{\"u}hler and Dirk Winkler and Thorsten Zenz and Sebastian B{\"o}ttcher and Matthias Ritgen and Myriam Mendila and Michael Dr. Kneba and H D{\"o}hner and S. Stilgenbauer},
  journal={The Lancet},

Excess mortality after treatment with fludarabine and cyclophosphamide in combination with alemtuzumab in previously untreated patients with chronic lymphocytic leukemia in a randomized phase 3 trial.

The results indicate that the FCCam regimen for the treatment of advanced chronic lymphocytic leukemia was not more effective than the FCR regimen and was associated with an unfavorable safety profile, representing a significant limitation of its use.

Bendamustine in combination with rituximab for previously untreated patients with chronic lymphocytic leukemia: a multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group.

  • K. FischerP. Cramer C. Wendtner
  • Medicine
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2012
Chemoimmunotherapy with BR is effective and safe in patients with previously untreated CLL, and 90.5% of patients were alive.

Rituximab maintenance after first-line therapy with rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) for chronic lymphocytic leukemia.

Investigation in a phase 2 clinical trial of rituximab maintenance therapy in the treatment of chronic lymphocytic leukemia found MRD status after R-FCM induction was the strongest predictor of PFS.

Second-line therapies of patients initially treated with fludarabine and cyclophosphamide or fludarabine, cyclophosphamide and rituximab for chronic lymphocytic leukemia within the CLL8 protocol of the German CLL Study Group

Abstract Updated results of the CLL8 trial confirm that the addition of rituximab to chemotherapy with fludarabine and cyclophosphamide (FC) leads to a prolongation of progression-free (PFS) and

Progress in the treatment of chronic lymphocytic leukemia: results of the German CLL8 trial

  • S. Molica
  • Medicine
    Expert review of anticancer therapy
  • 2011
The CLL8 trial has demonstrated that an association of rituximab, fludarabine and cyclophosphamide is effective in prolonging progression-free survival and overall survival of patients with symptomatic CLL, therefore establishing the new standard of treatment for physically fit patients.

A phase I-II trial of fludarabine, bendamustine and rituximab (FBR) in previously treated patients with CLL

Bine-elicited H2AX phosphorylation was not dose-dependent, but markedly increased after fludarabine, and bendamustine 30 mg/m2 was identified as the safe dose for phase II.



Fludarabine plus cyclophosphamide versus fludarabine alone in first-line therapy of younger patients with chronic lymphocytic leukemia.

First-line treatment with FC increases the response rates and the treatment-free interval in younger patients with advanced CLL and no difference in median overall survival has been observed.

Phase 2 study of a combined immunochemotherapy using rituximab and fludarabine in patients with chronic lymphocytic leukemia.

The combination of rituximab and fludarabine is feasible and effective in patients with B-CLL and the overall response rate was 87% and the median duration of response was 75 weeks.

Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab for relapsed and refractory chronic lymphocytic leukemia.

  • W. WierdaS. O'brien M. Keating
  • Medicine, Biology
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2005
FCR induced the highest CR rate reported in a clinical trial of previously treated patients with CLL, and molecular remissions were achieved in a third of patients achieving CR.

Phase III trial of fludarabine plus cyclophosphamide compared with fludarabine for patients with previously untreated chronic lymphocytic leukemia: US Intergroup Trial E2997.

  • I. FlinnD. Neuberg M. Tallman
  • Medicine, Biology
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2007
Fludarabine and cyclophosphamide produced an increase in OR and CR, and it improved PFS in patients with previously untreated CLL compared with fludarABine alone and was not associated with an increased in infectious toxicity.

Long-term results of the fludarabine, cyclophosphamide, and rituximab regimen as initial therapy of chronic lymphocytic leukemia.

In a multivariate analysis of patients receiving fludarabine-based therapy at the center, FCR therapy emerged as the strongest independent determinant of survival.

Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia.

FCR produced a high CR rate in previously untreated CLL, and most patients had no detectable disease on flow cytometry at the end of therapy.

Rituximab dose-escalation trial in chronic lymphocytic leukemia.

Rituximab has significant activity in patients with CLL at the higher dose levels and first-dose reactions were uncommon in patientswith CLL, even with high circulating lymphocyte counts, but were frequent in Patients with other mature B-cell leukemias in which CD20 surface expression is increased.

Rituximab therapy of patients with B-cell chronic lymphocytic leukemia.

The results suggest that rituximab has clinical activity in pretreated patients with B-CLL and toxicity is tolerable, and other modes of application and the combination with other agents need to be tested.