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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02477696




Registration number
NCT02477696
Ethics application status
Date submitted
12/06/2015
Date registered
23/06/2015
Date last updated
13/05/2024

Titles & IDs
Public title
Study of Acalabrutinib (ACP-196) Versus Ibrutinib in Previously Treated Participants With High Risk Chronic Lymphocytic Leukemia (CLL)
Scientific 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
Secondary ID [1] 0 0
2014-005530-64
Secondary ID [2] 0 0
ACE-CL-006
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Lymphocytic Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Acalabrutinib
Treatment: Drugs - Ibrutinib

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.

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.


Treatment: Drugs: Acalabrutinib
Participants will receive oral acalabrutinib as stated in arm description.

Treatment: Drugs: Ibrutinib
Participants will receive oral ibrutinib as stated in arm description.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS) Based on Independent Review Committee (IRC) Assessment
Timepoint [1] 0 0
Baseline (Days -28 to -1) through 55.2 months (maximum observed duration)
Secondary outcome [1] 0 0
Number of Participants With Treatment-emergent Infections Grade >= 3
Timepoint [1] 0 0
Day 1 through 83.5 months (maximum observed duration)
Secondary outcome [2] 0 0
Number of Participants With Treatment-emergent Richter's Transformation
Timepoint [2] 0 0
Day 1 through 83.5 months (maximum observed duration)
Secondary outcome [3] 0 0
Number of Participants With Treatment-emergent Atrial Fibrillation
Timepoint [3] 0 0
Day 1 through 83.5 months (maximum observed duration)
Secondary outcome [4] 0 0
Overall Survival (OS)
Timepoint [4] 0 0
Baseline (Days -28 to -1) through 83.7 months (maximum observed duration)
Secondary outcome [5] 0 0
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Timepoint [5] 0 0
Day 1 through 83.5 months (maximum observed duration)
Secondary outcome [6] 0 0
Number of Participants With Treatment-emergent Laboratory Abnormalities
Timepoint [6] 0 0
Day 1 through 83.5 months (maximum observed duration)
Secondary outcome [7] 0 0
Number of Participants With Abnormal Vital Signs Reported as TEAEs
Timepoint [7] 0 0
Day 1 through 83.5 months (maximum observed duration)
Secondary outcome [8] 0 0
Percentage of Participants With Lymphocytosis
Timepoint [8] 0 0
Day 1 through 83.5 months (maximum observed duration)
Secondary outcome [9] 0 0
Number of Participants With Electrocardiogram (ECG) Abnormality at Baseline
Timepoint [9] 0 0
Baseline (Days -28 to -1)
Secondary outcome [10] 0 0
Number of Participants With Shift From Baseline to Worst (Grade 3 and 4) Postbaseline in Eastern Cooperative Oncology Group (ECOG) Performance Status
Timepoint [10] 0 0
Baseline (Days -28 to -1) through 83.5 months (maximum observed duration)

Eligibility
Key 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.
Minimum age
No limit
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
28/07/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
3/01/2028
Actual
Sample size
Target
Accrual to date
Final
533
Recruitment in Australia
Recruitment state(s)
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Research Site - Darlinghurst
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Research Site - Frankston
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Research Site - Melbourne
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Research Site - St Leonards
Recruitment hospital [5] 0 0
Research Site - Waratah NSW
Recruitment hospital [6] 0 0
Research Site - Wollongong
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2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
3199 - Frankston
Recruitment postcode(s) [3] 0 0
3000 - Melbourne
Recruitment postcode(s) [4] 0 0
2065 - St Leonards
Recruitment postcode(s) [5] 0 0
2298 - Waratah NSW
Recruitment postcode(s) [6] 0 0
2500 - Wollongong
Recruitment outside Australia
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Acerta Pharma BV
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study is designed to evaluate progression-free survival (PFS) endpoint for acalabrutinib
versus (vs) ibrutinib in previously treated chronic lymphocytic leukemia.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02477696
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Acerta Clinical Trials
Address 0 0
1-888-292-9613
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02477696