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Bending the Curve Trial by Trial
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CLL4

Fludarabine With or Without Cyclophosphamide in Treating Patients With Advanced Chronic Lymphocytic Leukemia

Phase 3N = 375NCT00276848

Population
Previously untreated patients younger than 66 years with CLL, predominantly advanced disease.
Design
Randomised comparison, 1999 to 2003, of fludarabine (25 mg/m2 for 5 days) with fludarabine 30 mg/m2 plus cyclophosphamide 250 mg/m2 for 3 days (FC), repeated every 28 days to a maximum of 6 courses, as first-line treatment. ClinicalTrials.gov record (CLL4, 375 enrolled) matches the 375 patients in the paper.
Arms
  • Fludarabine (control): Fludarabine 25 mg/m2 for 5 days every 28 days, up to 6 courses
  • FC (experimental): Fludarabine 30 mg/m2 plus cyclophosphamide 250 mg/m2 for 3 days every 28 days, up to 6 courses
People
Eichhorst BF, German CLL Study Group
Δ CR rate+17 pointsΔ ORR+11 pointsΔ median PFS+28 months
Show the numbers
Results reported for CLL4
EndpointAnalysisFCFludarabineEffect
CR rateRandomised patients (analysis population not stated in the abstract)primaryEichhorst 200624%7%P<0.001Reported as complete remission rate.
ORRRandomised patients (analysis population not stated in the abstract)primaryEichhorst 200694%83%P=0.001Reported as overall response rate.
PFSRandomised patients (analysis population not stated in the abstract)primaryEichhorst 2006median 48 monthsmedian 20 monthsP=0.001Treatment-free survival 37 vs 25 months (P < .001). No difference in median overall survival had been observed at the time of the report.
Results reported for CLL4
EndpointAnalysisFCFludarabineEffect
CR rateRandomised patients (analysis population not stated in the abstract)primaryEichhorst 200624%7%P<0.001Reported as complete remission rate.
ORRRandomised patients (analysis population not stated in the abstract)primaryEichhorst 200694%83%P=0.001Reported as overall response rate.
PFSRandomised patients (analysis population not stated in the abstract)primaryEichhorst 2006median 48 monthsmedian 20 monthsP=0.001Treatment-free survival 37 vs 25 months (P < .001). No difference in median overall survival had been observed at the time of the report.
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%020406080100120Months (modelled)
  • Fludarabine (control)
  • FC (experimental)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsFludarabineFC
0100.0%100.0%
3035.4%64.8%
6012.5%42.0%
904.4%27.3%
1201.6%17.7%
Primary publication: Eichhorst BF, Busch R, Hopfinger G, Pasold R, Hensel M, Steinbrecher C, et al. Fludarabine plus cyclophosphamide versus fludarabine alone in first-line therapy of younger patients with chronic lymphocytic leukemia. Blood. 2006;107(3):885-91. PubMedDOI

Appears in

Sources

  1. Eichhorst BF, Busch R, Hopfinger G, Pasold R, Hensel M, Steinbrecher C, et al. Fludarabine plus cyclophosphamide versus fludarabine alone in first-line therapy of younger patients with chronic lymphocytic leukemia. Blood. 2006;107(3):885-91.

    PubMedDOI