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

Acerta Pharma

Status and phase: Active, not recruiting; Phase 3

Conditions: Chronic Lymphocytic Leukemia

Treatments: Drug: Ibrutinib; Drug: Acalabrutinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT02477696

2014-005530-64 (EudraCT Number)

ACE-CL-006

Details and patient eligibility

About

This study is designed to evaluate progression-free survival (PFS) endpoint for acalabrutinib versus (vs) ibrutinib in previously treated chronic lymphocytic leukemia.

Enrollment: 533 patients

Sex: All

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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533 participants in 2 patient groups

Acalabrutinib

Experimental group

Description:

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.

Treatment:

Drug: Acalabrutinib

Ibrutinib

Active Comparator group

Description:

Participants will receive oral ibrutinib 420 mg once daily (QD) until PD, or unacceptable toxicity, or other reasons for discontinuation, whichever occurrs first.

Treatment:

Drug: Ibrutinib