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CLL14

Comparison of the Treatments of Obinutuzumab + Venetoclax Versus Obinutuzumab + Chlorambucil in Patients With Chronic Lymphocytic Leukemia

Phase 3N = 432NCT02242942

Population
Previously untreated CLL with coexisting conditions (Cumulative Illness Rating Scale score above 6 or creatinine clearance below 70 ml per minute); median age 72 years.
Design
Open-label randomised phase 3 of fixed-duration venetoclax (12 cycles) with obinutuzumab (6 cycles) versus chlorambucil (12 cycles) with obinutuzumab (6 cycles). ClinicalTrials.gov lists 445 as actual enrolment; the publications report 432 randomised, 216 per group, and the paper's number is used.
Primary endpoint
PFS
Arms
  • Venetoclax-obinutuzumab (experimental, n = 216): Venetoclax for 12 cycles with obinutuzumab for 6 cycles
  • Chlorambucil-obinutuzumab (control, n = 216): Chlorambucil for 12 cycles with obinutuzumab for 6 cycles
People
Fischer K
PFSHR 0.35 (95% CI 0.23–0.53)Δ 24-month PFS+24.1 pointsPFSHR 0.40 (95% CI 0.31–0.52)Δ median PFS+39.8 monthsOSHR 0.69 (95% CI 0.48–1.01)Δ 72-month OS+9.5 points
Show the numbers
Results reported for CLL14
EndpointAnalysisVenetoclax-obinutuzumabChlorambucil-obinutuzumabEffect
PFSAll randomised patients (216 per group)primarymedian follow-up 28.1 monthsFischer 201988.2% at 2 y (83.7–92.6%)64.1% at 2 y (57.4–70.8%)HR 0.35 (95% CI 0.23–0.53)P<0.001Investigator-assessed; 30 primary-endpoint events with venetoclax-obinutuzumab and 77 with chlorambucil-obinutuzumab.
PFSAll randomised patients (216 per group)long term-updatemedian follow-up 76.4 monthsAl-Sawaf 2024median 76.2 monthsmedian 36.4 monthsHR 0.40 (95% CI 0.31–0.52)P<0.0001Six-year results of CLL14.
OSAll randomised patients (216 per group)long term-updatemedian follow-up 76.4 monthsAl-Sawaf 202478.7% at 6 y69.2% at 6 yHR 0.69 (95% CI 0.48–1.01)P=0.052Overall survival was a key secondary endpoint.
Results reported for CLL14
EndpointAnalysisVenetoclax-obinutuzumabChlorambucil-obinutuzumabEffect
PFSAll randomised patients (216 per group)primarymedian follow-up 28.1 monthsFischer 201988.2% at 2 y (83.7–92.6%)64.1% at 2 y (57.4–70.8%)HR 0.35 (95% CI 0.23–0.53)P<0.001Investigator-assessed; 30 primary-endpoint events with venetoclax-obinutuzumab and 77 with chlorambucil-obinutuzumab.
PFSAll randomised patients (216 per group)long term-updatemedian follow-up 76.4 monthsAl-Sawaf 2024median 76.2 monthsmedian 36.4 monthsHR 0.40 (95% CI 0.31–0.52)P<0.0001Six-year results of CLL14.
OSAll randomised patients (216 per group)long term-updatemedian follow-up 76.4 monthsAl-Sawaf 202478.7% at 6 y69.2% at 6 yHR 0.69 (95% CI 0.48–1.01)P=0.052Overall survival was a key secondary endpoint.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFSPFSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS0.350.23–0.53
PFS0.40.31–0.52
OS0.690.48–1.01
Illustrative — modelled from reported values, not trial data. PFS, long term-update.
0%25%50%75%100%050100150Months (modelled)
  • Venetoclax-obinutuzumab (experimental)
  • Chlorambucil-obinutuzumab (control)

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

Data table (modelled values)
MonthsVenetoclax-obinutuzumabChlorambucil-obinutuzumab
0100.0%100.0%
4864.6%40.1%
9542.1%16.4%
14327.2%6.6%
19117.6%2.6%
Primary publication: Fischer K, Al-Sawaf O, Bahlo J, Fink AM, Tandon M, Dixon M, et al. Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions. N Engl J Med. 2019;380(23):2225-2236. PubMedDOI

Appears in

Sources

  1. Fischer K, Al-Sawaf O, Bahlo J, Fink AM, Tandon M, Dixon M, et al. Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions. N Engl J Med. 2019;380(23):2225-2236.

    PubMedDOI

  2. Al-Sawaf O, Robrecht S, Zhang C, Olivieri S, Chang YM, Fink AM, et al. Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the randomized phase 3 CLL14 study. Blood. 2024;144(18):1924-1935.

    PubMedDOI