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

Chronic Lymphocytic Leukemia Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02477696
• Other study ID #: ACE-CL-006
• Secondary ID: 2014-005530-64
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 28, 2015
• Est. completion date: January 3, 2028

Study information

• Verified date: May 2024
• Source: Acerta Pharma BV
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 533
• Est. completion date: January 3, 2028
• Est. primary completion date: September 15, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Drug:
• Acalabrutinib
Participants will receive oral acalabrutinib as stated in arm description.
• Ibrutinib
Participants will receive oral ibrutinib as stated in arm description.

Locations

Country	Name	City	State
Australia	Research Site	Darlinghurst
Australia	Research Site	Frankston
Australia	Research Site	Melbourne
Australia	Research Site	St Leonards
Australia	Research Site	Waratah NSW
Australia	Research Site	Wollongong
Belgium	Research Site	Brugge
Belgium	Research Site	Bruxelles
Belgium	Research Site	Ghent
Belgium	Research Site	Leuven
Belgium	Research Site	Yvoir
Denmark	Research Site	Aalborg
Denmark	Research Site	Indgang 27B
France	Research Site	Bobigny
France	Research Site	Creteil
France	Research Site	Pierre-Benite
France	Research Site	Rennes Cedex
France	Research Site	Rouen
France	Research Site	Toulouse Cedex
Germany	Research Site	München
Germany	Research Site	Ulm
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Debrecen
Hungary	Research Site	Kaposvár
Israel	Research Site	Haifa
Israel	Research Site	Haifa
Israel	Research Site	Haifa
Israel	Research Site	Jerusalem
Israel	Research Site	Nahariya
Israel	Research Site	Petah Tikvah
Israel	Research Site	Tel Hashomer
Israel	Research Site	Tiberias
Italy	Research Site	Bologna
Italy	Research Site	Cagliari
Italy	Research Site	Cona
Italy	Research Site	Firenze
Italy	Research Site	Meldola
Italy	Research Site	Milan
Italy	Research Site	Milano
Italy	Research Site	Modena
Italy	Research Site	Ravenna
Italy	Research Site	Rome
Netherlands	Research Site	Almere
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Blaricum
Netherlands	Research Site	Breda
Netherlands	Research Site	Delft
Netherlands	Research Site	Dordrecht
Netherlands	Research Site	Geleen
Netherlands	Research Site	Groningen
Netherlands	Research Site	Haarlem
Netherlands	Research Site	Leiden
Netherlands	Research Site	Rotterdam
Netherlands	Research Site	Rotterdam
Netherlands	Research Site	Utrecht
Netherlands	Research Site	Zutphens
New Zealand	Research Site	Addington
New Zealand	Research Site	Auckland
New Zealand	Research Site	Tauranga
Poland	Research Site	Bydgoszcz
Poland	Research Site	Gdansk
Poland	Research Site	Gdynia
Poland	Research Site	Kraków
Poland	Research Site	Lodz
Poland	Research Site	Olsztyn
Poland	Research Site	Opole
Poland	Research Site	Slupsk
Poland	Research Site	Wroclaw
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Majadahonda
Spain	Research Site	Murcia
Spain	Research Site	Santander
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Instabul
Turkey	Research Site	Istanbul
Turkey	Research Site	Izmir
Turkey	Research Site	Izmir
Turkey	Research Site	Kayseri
United Kingdom	Research Site	Birmingham
United Kingdom	Research Site	Bournemouth
United Kingdom	Research Site	Cambridge
United Kingdom	Research Site	Cardiff
United Kingdom	Research Site	Greater London
United Kingdom	Research Site	Hull
United Kingdom	Research Site	Leeds
United Kingdom	Research Site	Leicester
United Kingdom	Research Site	Liverpool
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Nottingham
United Kingdom	Research Site	Plymouth
United Kingdom	Research Site	Southampton
United Kingdom	Research Site	Surrey
United States	Research Site	Anaheim	California
United States	Research Site	Athens	Georgia
United States	Research Site	Berkeley	California
United States	Research Site	Billings	Montana
United States	Research Site	Charlottesville	Virginia
United States	Research Site	Columbus	Ohio
United States	Research Site	Duarte	California
United States	Research Site	Durham	North Carolina
United States	Research Site	Hackensack	New Jersey
United States	Research Site	Harvey	Illinois
United States	Research Site	Houston	Texas
United States	Research Site	Jacksonville	Florida
United States	Research Site	La Jolla	California
United States	Research Site	Lake Success	New York
United States	Research Site	Los Angeles	California
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	New Hyde Park	New York
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	Northwest WA	Wisconsin
United States	Research Site	Palo Alto	California
United States	Research Site	Peoria	Illinois
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Phoenix	Arizona
United States	Research Site	Rochester	Minnesota
United States	Research Site	Round Rock	Texas
United States	Research Site	Santa Rosa	California
United States	Research Site	Tacoma	Washington
United States	Research Site	Tampa	Florida
United States	Research Site	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Acerta Pharma BV

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Denmark,  France,  Germany,  Hungary,  Israel,  Italy,  Netherlands,  New Zealand,  Poland,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS) Based on Independent Review Committee (IRC) Assessment	The PFS is defined as the time from date of randomization to the date of first IRC-assessed PD or death due to any cause, whichever occurred first. PD (per International Workshop on Chronic Lymphocytic Leukemia [iwCLL] 2008 criteria): Lymphocytes >= 50% increase over baseline, or >= 50% increase in lymphadenopathy/hepatomegaly/splenomegaly, or >= 50% platelets or > 2 g/dL hemoglobin decreases from baseline secondary to chronic lymphocytic leukemia (CLL). The PFS is assessed using the Kaplan-Meier method.	Baseline (Days -28 to -1) through 55.2 months (maximum observed duration)
Secondary	Number of Participants With Treatment-emergent Infections Grade >= 3	Number of participants with treatment-emergent infections Grade >=3 are reported.	Day 1 through 83.5 months (maximum observed duration)
Secondary	Number of Participants With Treatment-emergent Richter's Transformation	Richter's transformation is defined as the occurrence of an aggressive lymphoma in participants with a previous or concomitant diagnosis of CLL. Richter's transformation was assessed by central pathology. Number of participants with treatment-emergent Richter's transformation are reported.	Day 1 through 83.5 months (maximum observed duration)
Secondary	Number of Participants With Treatment-emergent Atrial Fibrillation	Number of participants with treatment-emergent atrial fibrillation (including atrial flutter) are reported.	Day 1 through 83.5 months (maximum observed duration)
Secondary	Overall Survival (OS)	The OS is defined as the time from date of randomization to date of death due to any cause. The OS is assessed using the Kaplan-Meier method.	Baseline (Days -28 to -1) through 83.7 months (maximum observed duration)
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.	Day 1 through 83.5 months (maximum observed duration)
Secondary	Number of Participants With Treatment-emergent Laboratory Abnormalities	Number of participants with treatment-emergent laboratory abnormalities are reported. Laboratory abnormality is defined as any abnormal finding during analysis of hematology and serum chemistry.	Day 1 through 83.5 months (maximum observed duration)
Secondary	Number of Participants With Abnormal Vital Signs Reported as TEAEs	Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (body temperature, blood pressure, heart rate, and respiratory rate).	Day 1 through 83.5 months (maximum observed duration)
Secondary	Percentage of Participants With Lymphocytosis	Percentage of participants with at least one occurrence of treatment-related lymphocytosis defined as an elevation in ALC of >= 50% compared with baseline and a postbaseline assessment of > 5000/µL in the peripheral blood are reported.	Day 1 through 83.5 months (maximum observed duration)
Secondary	Number of Participants With Electrocardiogram (ECG) Abnormality at Baseline	Number of participants with ECG abnormality at baseline are reported.	Baseline (Days -28 to -1)
Secondary	Number of Participants With Shift From Baseline to Worst (Grade 3 and 4) Postbaseline in Eastern Cooperative Oncology Group (ECOG) Performance Status	The ECOG performance status assessed participant's performance status on 5 point scale: 0=Fully active/able to carry on all pre-disease activities without restriction; 1=restricted in physically strenuous activity, ambulatory/able to carry out light or sedentary work; 2=ambulatory (>50% of waking hours), capable of all self-care, unable to carry out any work activities; 3=capable of only limited self care, confined to bed/chair >50% of waking hrs; 4=completely disabled, cannot carry on any self care, totally confined to bed/chair; 5=death. Number of participants with shift from baseline (Days -28 to -1) to worst Grade 3 and 4 in ECOG performance status are reported.	Baseline (Days -28 to -1) through 83.5 months (maximum observed duration)

External Links

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