Study of Acalabrutinib (ACP-196) Versus Ibrutinib in Previously Treated Participants with High Risk Chronic Lymphocytic Leukemia (CLL)

Study identifier:ACE-CL-006

ClinicalTrials.gov identifier:NCT02477696

EudraCT identifier:2014-005530-64

CTIS identifier:N/A

Recruitment Complete

Official Title

A Randomized, Multicenter, Open-Label, Non-Inferiority, Phase III Study of Acalabrutinib (ACP-196) versus Ibrutinib in Previously Treated Subjects with High Risk Chronic Lymphocytic Leukemia

Medical condition

Chronic Lymphocytic Leukemia

Phase

Phase 3

Healthy volunteers

Study drug

Acalabrutinib, Ibrutinib

Sex

All

Actual Enrollment

533

Study type

Interventional

Age

n/a - n/a

Date

Study Start Date: 28 Jul 2015

Primary Completion Date: 15 Sept 2020

Estimated Study Completion Date: 03 Jan 2028

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: Single Blind
Primary Purpose: Treatment

Verification:

Verified 01 Jan 2024 by AcertaPharma

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

- Men and women ≥ 18 years of age.
- ECOG performance status of 0 to 2.
- Diagnosis of CLL.
- Must have ≥ 1 of the following high-risk prognostic factors:
*Presence of 17p del by central laboratory.
*Presence of 11q del by central laboratory.
- Active disease meeting ≥ 1 of the following IWCLL 2008 criteria for requiring treatment
- Must have received ≥ 1 prior therapies for CLL.
- Meet the following laboratory parameters:
*Absolute neutrophil count (ANC) ≥ 750 cells/μL or ≥ 500 cells/μL in participants with documented bone marrow involvement, and independent of growth factor support 7 days before assessment.
*Platelet count ≥ 30,000 cells/μL without transfusion support 7 days before assessment. Participants with transfusion-dependent thrombocytopenia are excluded.
* Serum aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) ≤ 3.0 x upper limit of normal (ULN).
*Total bilirubin ≤ 1.5 x ULN.
*Estimated creatinine clearance ≥ 30 mL/min.

Exclusion Criteria

- 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.
- Prior exposure to ibrutinib or to a B-cell receptor (BCR) inhibitor or a B-cell lymphoma-2 (BCL-2) inhibitor.
- Received any chemotherapy, external beam radiation therapy, anticancer antibodies, or investigational drug within 30 days before first dose of study drug.
- Prior radio- or toxin-conjugated antibody therapy.
- Prior allogeneic stem cell or autologous transplant.
- Major surgery within 4 weeks before first dose of study drug.
- Prior malignancy, except for adequately treated lentigo maligna 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 within 6 months of screening.
- Known history of infection with human immunodeficiency virus (HIV).
- History of stroke or intracranial hemorrhage within 6 months before randomization.
- History of bleeding diathesis.
- Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists within 7 days of first dose of study drug.
- Requires treatment with a strong cytochrome P450 3A (CYP3A) inhibitor/inducer.

No locations available

Arms	Assigned Interventions
Experimental: Acalabrutinib Participants will receive oral acalabrutinib 100 mg twice daily (BID) until disease progression (PD), or unacceptable toxicity, or other reasons for discontinuation, whichever occurs first.	Drug: Acalabrutinib Participants will receive oral acalabrutinib as stated in arm description. Other Name: ACP-196
Active Comparator: Ibrutinib Participants will receive oral ibrutinib 420 mg once daily (QD) until PD, or unacceptable toxicity, or other reasons for discontinuation, whichever occurrs first.	Drug: Ibrutinib Participants will receive oral ibrutinib as stated in arm description.

Documents available

Redacted CSR Synopsis
Download
Redacted CSP
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Redacted SAP
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Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

Investigators

Principal Investigator

Acerta Clinical Trials

1-888-292-9613