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CLL11

CLL11: An Open-label, Multi-center, Three Arm Randomized Study to Investigate the Safety and Efficacy on Progression-free Survival of RO5072759 + Chlorambucil (GClb) Compared to Rituximab + Chlorambucil (RClb) or Chlorambucil (Clb) Alone in Previously Untreated CLL Patients With Comorbidities

Phase 3N = 781NCT01010061

Population
Previously untreated CLL with coexisting conditions: Cumulative Illness Rating Scale (CIRS) score above 6 (range 0 to 56) or estimated creatinine clearance of 30 to 69 ml per minute. Median age 73 years.
Design
Three-arm randomised trial: chlorambucil, obinutuzumab plus chlorambucil, or rituximab plus chlorambucil. Primary endpoint investigator-assessed PFS. The abstract reports 781 randomised patients; ClinicalTrials.gov lists 787 enrolled (the paper's number is used here). The registry title carries the label Stage 1a; the stage structure was not read from the full text.
Primary endpoint
PFS
Arms
  • Chlorambucil (control): Chlorambucil alone
  • Obinutuzumab-chlorambucil (experimental): Obinutuzumab plus chlorambucil
  • Rituximab-chlorambucil (experimental): Rituximab plus chlorambucil
People
Goede V
PFSHR 0.18 (95% CI 0.13–0.24)Δ median PFS+15.6 monthsPFSHR 0.44 (95% CI 0.34–0.57)Δ median PFS+5.2 monthsPFSHR 0.39 (95% CI 0.31–0.49)OSHR 0.41 (95% CI 0.23–0.74)
Show the numbers
Results reported for CLL11
EndpointAnalysisObinutuzumab-chlorambucil / Rituximab-chlorambucilChlorambucilEffect
PFSRandomised patients (781; analysis population not stated in the abstract)primaryGoede 2014median 26.7 monthsmedian 11.1 monthsHR 0.18 (95% CI 0.13–0.24)P<0.001Primary endpoint, investigator-assessed.
PFSRandomised patients (781; analysis population not stated in the abstract)primaryGoede 2014median 16.3 monthsmedian 11.1 monthsHR 0.44 (95% CI 0.34–0.57)P<0.001Investigator-assessed.
PFSRandomised patients (781; analysis population not stated in the abstract)primaryGoede 2014——HR 0.39 (95% CI 0.31–0.49)P<0.001Head-to-head comparison of the two antibody arms; medians for this comparison are not given in the abstract.
OSRandomised patients (781; analysis population not stated in the abstract)primaryGoede 2014——HR 0.41 (95% CI 0.23–0.74)P=0.002Obinutuzumab-chlorambucil versus chlorambucil alone. The abstract does not describe the analysis as interim or final.
CR rateRandomised patients (781; analysis population not stated in the abstract)primaryGoede 201420.7%—Obinutuzumab-chlorambucil versus rituximab-chlorambucil. The abstract also reports a higher molecular response rate with obinutuzumab-chlorambucil, without numbers.
Results reported for CLL11
EndpointAnalysisObinutuzumab-chlorambucil / Rituximab-chlorambucilChlorambucilEffect
PFSRandomised patients (781; analysis population not stated in the abstract)primaryGoede 2014median 26.7 monthsmedian 11.1 monthsHR 0.18 (95% CI 0.13–0.24)P<0.001Primary endpoint, investigator-assessed.
PFSRandomised patients (781; analysis population not stated in the abstract)primaryGoede 2014median 16.3 monthsmedian 11.1 monthsHR 0.44 (95% CI 0.34–0.57)P<0.001Investigator-assessed.
PFSRandomised patients (781; analysis population not stated in the abstract)primaryGoede 2014——HR 0.39 (95% CI 0.31–0.49)P<0.001Head-to-head comparison of the two antibody arms; medians for this comparison are not given in the abstract.
OSRandomised patients (781; analysis population not stated in the abstract)primaryGoede 2014——HR 0.41 (95% CI 0.23–0.74)P=0.002Obinutuzumab-chlorambucil versus chlorambucil alone. The abstract does not describe the analysis as interim or final.
CR rateRandomised patients (781; analysis population not stated in the abstract)primaryGoede 201420.7%—Obinutuzumab-chlorambucil versus rituximab-chlorambucil. The abstract also reports a higher molecular response rate with obinutuzumab-chlorambucil, without numbers.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFSPFSPFSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS0.180.13–0.24
PFS0.440.34–0.57
PFS0.390.31–0.49
OS0.410.23–0.74
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%0102030405060Months (modelled)
  • Chlorambucil (control)
  • Obinutuzumab-chlorambucil (experimental)

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

Data table (modelled values)
MonthsChlorambucilObinutuzumab-chlorambucil
0100.0%100.0%
1734.6%64.3%
3312.7%42.5%
504.4%27.3%
671.5%17.6%
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%010203040Months (modelled)
  • Chlorambucil (control)
  • Rituximab-chlorambucil (experimental)

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

Data table (modelled values)
MonthsChlorambucilRituximab-chlorambucil
0100.0%100.0%
1053.6%65.4%
2028.7%42.7%
3114.4%26.8%
417.7%17.5%
Primary publication: Goede V, Fischer K, Busch R, Engelke A, Eichhorst B, Wendtner CM, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014;370(12):1101-10. PubMedDOI

Appears in

Sources

  1. Goede V, Fischer K, Busch R, Engelke A, Eichhorst B, Wendtner CM, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014;370(12):1101-10.

    PubMedDOI