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AMPLIFY

Study of Acalabrutinib (ACP-196) in Combination With Venetoclax (ABT-199), With and Without Obinutuzumab (GA101) Versus Chemoimmunotherapy for Previously Untreated CLL

Phase 3N = 867NCT03836261

Population
Previously untreated CLL, ECOG performance status 0 to 2, without 17p deletion or TP53 mutation; median age 61 years.
Design
Open-label randomised phase 3, 1:1:1: acalabrutinib-venetoclax (acalabrutinib in cycles 1 to 14, venetoclax in cycles 3 to 14), acalabrutinib-venetoclax-obinutuzumab (plus obinutuzumab in cycles 2 to 7), or investigator's choice of FCR or BR (cycles 1 to 6). The primary comparison was acalabrutinib-venetoclax versus chemoimmunotherapy. ClinicalTrials.gov lists 984 as actual enrolment; the paper reports 867 randomised, and the paper's number is used.
Primary endpoint
PFS
Arms
  • Acalabrutinib-venetoclax (experimental, n = 291): Acalabrutinib cycles 1 to 14, venetoclax cycles 3 to 14
  • Acalabrutinib-venetoclax-obinutuzumab (experimental, n = 286): Acalabrutinib-venetoclax plus obinutuzumab in cycles 2 to 7
  • Chemoimmunotherapy (control, n = 290): Investigator's choice of FCR (143 patients) or BR (147 patients), cycles 1 to 6
People
Brown JR
PFSHR 0.65 (95% CI 0.49–0.87)Δ 36-month PFS+10 pointsΔ 36-month PFS+16.6 pointsΔ 36-month OS+8.2 points
Show the numbers
Results reported for AMPLIFY
EndpointAnalysisAcalabrutinib-venetoclax / Acalabrutinib-venetoclax-obinutuzumabChemoimmunotherapyEffect
PFSIntention-to-treat population (867 randomised)primarymedian follow-up 40.8 monthsBrown 202576.5% at 3 y66.5% at 3 yHR 0.65 (95% CI 0.49–0.87)P=0.004Progression-free survival assessed by blinded independent central review; primary comparison.
PFSIntention-to-treat population (867 randomised)primarymedian follow-up 40.8 monthsBrown 202583.1% at 3 y66.5% at 3 yP<0.001Acalabrutinib-venetoclax-obinutuzumab versus chemoimmunotherapy; the abstract gives a P value but no hazard ratio for this comparison. This is not the primary comparison, which was acalabrutinib-venetoclax versus chemoimmunotherapy.
OSRandomised patients (867); the abstract does not state the analysis population for overall survivalprimarymedian follow-up 40.8 monthsBrown 202594.1% at 3 y85.9% at 3 yThe abstract gives no hazard ratio or P value for overall survival. Death from COVID-19 was reported in 10, 25 and 21 patients in the three groups.
Results reported for AMPLIFY
EndpointAnalysisAcalabrutinib-venetoclax / Acalabrutinib-venetoclax-obinutuzumabChemoimmunotherapyEffect
PFSIntention-to-treat population (867 randomised)primarymedian follow-up 40.8 monthsBrown 202576.5% at 3 y66.5% at 3 yHR 0.65 (95% CI 0.49–0.87)P=0.004Progression-free survival assessed by blinded independent central review; primary comparison.
PFSIntention-to-treat population (867 randomised)primarymedian follow-up 40.8 monthsBrown 202583.1% at 3 y66.5% at 3 yP<0.001Acalabrutinib-venetoclax-obinutuzumab versus chemoimmunotherapy; the abstract gives a P value but no hazard ratio for this comparison. This is not the primary comparison, which was acalabrutinib-venetoclax versus chemoimmunotherapy.
OSRandomised patients (867); the abstract does not state the analysis population for overall survivalprimarymedian follow-up 40.8 monthsBrown 202594.1% at 3 y85.9% at 3 yThe abstract gives no hazard ratio or P value for overall survival. Death from COVID-19 was reported in 10, 25 and 21 patients in the three groups.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS0.650.49–0.87
Primary publication: Brown JR, Seymour JF, Jurczak W, Aw A, Wach M, Illes A, et al. Fixed-Duration Acalabrutinib Combinations in Untreated Chronic Lymphocytic Leukemia. N Engl J Med. 2025;392(8):748-762. PubMedDOI

Appears in

Sources

  1. Brown JR, Seymour JF, Jurczak W, Aw A, Wach M, Illes A, et al. Fixed-Duration Acalabrutinib Combinations in Untreated Chronic Lymphocytic Leukemia. N Engl J Med. 2025;392(8):748-762.

    PubMedDOI