Study Design

Head-to-head trial of acalabrutinib versus ibrutinib in R/R CLL1,2

Study Design2

Study Design2

aBy central laboratory testing; bcontinued until disease progression or unacceptable toxicity

Primary Endpoint1

  • Non-inferiority on IRC assessed PFS

Secondary Endpoints1

  • Incidence of any grade atrial fibrillation/flutter
  • Incidence of grade ≥3 infection
  • Incidence of Richter transformation
  • Overall survival

Key Eligibility Criteria

Key Eligibility Criteria

Key eligibility criteria for ELEVATE-RR1
 Key Inclusion CriteriaKey Exclusion Criteria
Men and women aged ≥18 yearsKnown CNS lymphoma or leukemia
ECOG performance status 0-2Significant cardiovascular diseasea
Diagnosis of CLL: active disease meeting ≥1 of the iwCLL 2008 criteria for requiring treatmentHistory of bleeding diathesis
Must have received ≥1 prior therapies for CLLRequiring or receiving anticoagulation with warfarin or equivalent vitamin K antagonists within 7 days of first dose of study drug
 History of stroke or intracranial hemorrhage
 Prior exposure to ibrutinib, BCR inhibitor or a BCL-2 inhibitor
aDefined as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or corrected QT interval (QTc) > 480 msec at screening.

Hierarchical Testing Schema

Hierarchical Testing Schema

Hierarchical testing strategy for endpoints1

Hierarchical testing strategy for endpoints1

Note: NI on the primary endpoint (IRC-assessed PFS) assessed using a Cox proportional-hazards model stratified by del(17p) status and no. prior therapies (1–3 vs ≥4). Superiority on secondary endpoints was tested hierarchically at a 2-sided 0.05 significance level: aAfib/flutter, Gr≥3 infection, and RT: Cochran-Mantel-Haenszel test adjusted for del(17p) status and no. prior therapies (1–3 vs ≥4); bOS: KM methods and stratified log-rank test.

Abbreviations

Afib/flutter = atrial fibrillation/flutter

;

BCL2 = B-cell lymphoma 2

;

BCR = B cell receptor

;

BID = twice daily

;

CI = confidence interval

;

CLL = chronic lymphocytic leukemia

;

CNS = central nervous system

;

ECOG PS = Eastern Cooperative Oncology Group performance status

;

Gr = grade

;

HR = hazard ratio

;

IRC = independent review committee 

;

iwCLL = international workshop on CLL

;

KM = Kaplan-Meier

;

NI = non-inferiority

;

OS = overall survival 

;

PFS = progression-free survival 

;

PO = orally

;

QD = once daily

;

R = randomization

;

RT = Richter transformation

References

1. Byrd JC, Hillmen P, Ghia P, et al. First results of a head-to-head trial of acalabrutinib versus ibrutinib in previously treated chronic lymphocytic lymphoma [oral presentation]. Presented at: American Society of Clinical Oncology (ASCO) Virtual Annual Meeting; June 4-8, 2021. Chicago, IL. Abstract 7500.
2. Byrd JC, Hillmen P, Ghia P, et al.  Acalabrutinib versus ibrutinib in previously treated chronic lymphocytic leukemia: Results of the first randomized Phase III trial. J. Clin. Oncol. 2021. https://doi.org/10.1200/JCO.21.01210.

Document ID: b5f1a3c0-28eb-4186-8709-e3ddba7b6695
Last updated: 17-April-2023