Study Design & Eligibility Criteria

Study Design

A Phase III, Study of Acalabrutinib Combined with Obinutuzumab (O) or Alone vs O Plus Chlorambucil (Clb) in patients with Treatment-Naïve (TN) Chronic Lymphocytic Leukemia (CLL)1,2

Study Design1

Study Design1

Primary End Point1,2

  • PFS by IRC (Acalabrutinib-O vs O-Clb)

Secondary End Points1,2

  • PFS by IRC (A vs O-Clb)
  • PFS (INV-assessed)
  • ORR (IRC and INV-assessed)
  • TTNT
  • OS
  • uMRD2
  • Safety

Note: After interim analysis, PFS assessments were by investigator only2

Key Eligibility Criteria

Key eligibility criteria for ELEVATE-TN 3

Key Inclusion Criteria1,3
Men and women ≥65 years old OR > 18 and <65 years old with coexisting conditions (CIRS-G score >6, creatinine clearance 30–69 mL/min)
ECOG status ≤ 2
Diagnosis of CLL
Active disease meeting ≥ 1 of the following IWCLL 2008 criteria for requiring treatment

Meet the following laboratory parameters:

  • ANC ≥ 750 cells/μL, or ≥ 500 cells/μL in subjects with documented bone marrow involvement, and independent of growth factor support 7 days before assessment
  • Platelet count ≥ 50,000 cells/μL, or ≥ 30,000 cells/μL in subjects with documented bone marrow involvement, and without transfusion support 7 days before assessment. Subjects with transfusion-dependent thrombocytopenia are excluded
  • Serum AST and ALT/SGPT ≤ 3.0 × ULN
  • Total bilirubin ≤ 1.5 × ULN
  • Estimated creatinine clearance ≥ 30 mL/min
Key Exclusion Criteria1,3
Any prior systemic treatment for CLL
Known CNS lymphoma or leukemia
Known prolymphocytic leukemia or history of, or currently suspected Richter's syndrome
Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura
Major surgery within 4 weeks before first dose of study drug
Prior malignancy, except for adequately treated lentigo malignant melanoma, non-melanomatous skin cancer, in situ cervical carcinoma, or other malignancy treated with no evidence of active disease > 3 years before Screening and at low risk for recurrence
Significant cardiovascular disease (QTc >480) within 6 months of screening. Patients with previous atrial fibrillation were allowed if controlled for 6 months
Known history of infection with HIV
History of stroke or intracranial hemorrhage within 6 months before randomization
Known history of a bleeding diathesis
Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists within 7 days of first dose of study drug. Patients on antiplatelets and other anticoagulants were allowed.

Abbreviations

A = acalabrutinib

;

ALT = alanine aminotransferase

;

ANC = absolute neutrophil count

;

AST = aspartate aminotransferase

;

BID = twice daily

;

CIRS-G = Cumulative Illness Rating Scale-Geriatric

;

Clb = chlorambucil

;

CLL = chronic lymphocytic leukemia

;

CNS = central nervous system

;

CrCl = creatinine clearance

;

ECOG = Eastern Cooperative Oncology Group

;

HIV = human immunodeficiency virus

;

IRC = independent review committee 

;

INV = investigator

;

IV = intravenous

;

IwCLL = international workshop on CLL

;

O = obinutuzumab

;

ORR = overall response rate

;

OS = overall survival 

;

PD = progressive disease

;

PFS = progression-free survival 

;

R = randomize

;

SGPT = serum glutamic pyruvic transaminase

;

TN = treatment-naïve

;

TTNT = time to next treatment

;

ULN = upper limit of normal

;

uMRD = undetectable minimal residual disease

References

1. Sharman JP, Egyed M, Jurczak W et al. Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzumab for treatment-nave chronic lymphocytic leukemia (ELEVATE TN): a randomized, controlled phase 3 trial [article and supplementary appendix]. Lancet. 2020;395:1278-91.
2. Sharman J, Egyed M, Jurczak W, et al. Acalabrutinib with or without obinutuzumab versus obinutuzumab with chlorambucil in treatment-naive chronic lymphocytic leukemia: ELEVATE-TN 4-year follow-up [oral presentation]. Presented at: American Society of Clinical Oncology (ASCO) Virtual Annual Meeting; June 4-8, 2021. Chicago, IL. Abs 7509.
3. Acerta Pharma BV. Elevate CLL TN: study of obinutuzumab + chlorambucil, acalabrutinib (ACP-196) + obinutuzumab, and acalabrutinib in subjects with previously untreated CLL. ClinicalTrials.gov website. https://clinicaltrials.gov/ct2/show/NCT02475681.

Document ID: 780f9b60-d375-4516-97d6-9ba58f025de4
Last updated: 17-April-2023

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