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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02477696
Ethics application status
Date submitted
12/06/2015
Date registered
23/06/2015

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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Darlinghurst
Recruitment hospital [2] 0 0
Research Site - Frankston
Recruitment hospital [3] 0 0
Research Site - Melbourne
Recruitment hospital [4] 0 0
Research Site - St Leonards
Recruitment hospital [5] 0 0
Research Site - Waratah NSW
Recruitment hospital [6] 0 0
Research Site - Wollongong
Recruitment postcode(s) [1] 0 0
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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United States of America
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Arizona
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California
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Illinois
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Kansas
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Minnesota
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Montana
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New Jersey
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New York
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North Carolina
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Ohio
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Pennsylvania
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Texas
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Virginia
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Washington
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Wisconsin
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Belgium
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Brugge
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Belgium
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Bruxelles
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Belgium
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Ghent
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Leuven
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Yvoir
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Aalborg
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Rouen
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Germany
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Ulm
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Debrecen
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Haifa
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Jerusalem
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Tel Hashomer
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Tiberias
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Cona
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Meldola
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Milano
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Modena
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Santander
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Instabul
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Istanbul
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Izmir
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Kayseri
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United Kingdom
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Birmingham
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Bournemouth
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Cambridge
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Cardiff
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Hull
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Leicester
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Manchester
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Nottingham
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Plymouth
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Southampton
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United Kingdom
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Surrey

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Acerta Pharma BV
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Available to whom?
When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.