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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04008706




Registration number
NCT04008706
Ethics application status
Date submitted
19/06/2019
Date registered
5/07/2019

Titles & IDs
Public title
Acalabrutinib Safety Study in Untreated and Relapsed or Refractory Chronic Lymphocytic Leukemia Patients
Scientific title
A Phase 3b, Multicenter, Open-Label, Single-Arm Study of Acalabrutinib (ACP-196) in Subjects With Chronic Lymphocytic Leukemia.
Secondary ID [1] 0 0
2019-001573-89
Secondary ID [2] 0 0
D8220C00008
Universal Trial Number (UTN)
Trial acronym
ASSURE
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

Experimental: Acalabrutinib - Participants will be enrolled into 3 cohorts. In the treatment-naive cohort, a minimum of 300 participants with treatment-naïve chronic lymphocytic leukemia will be enrolled. In the relapsed/refractory cohort, approximately 200 participants with relapsed/refractory chronic lymphocytic leukemia will be enrolled. In the prior ibrutinib cohort, approximately 40 participants with Prior ibrutinib therapy will be enrolled.


Treatment: Drugs: Acalabrutinib
Acalabrutinib will be administered as one 100 mg capsule taken orally, twice daily with 8 ounces (approximately 240 mL) of water.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with adverse events
Timepoint [1] 0 0
From screening to safety follow-up period (approximately 30 days from last dose)
Secondary outcome [1] 0 0
Overall response (OR)
Timepoint [1] 0 0
1 year after initial dose of study drug
Secondary outcome [2] 0 0
Duration of response (DOR)
Timepoint [2] 0 0
The time from the first objective response to the time of documented disease progression or death due to any cause, whichever occurs first within the time period to complete up to 48 cycles of treatment (each cycle is 28 days)
Secondary outcome [3] 0 0
Progression-free survival (PFS)
Timepoint [3] 0 0
The interval from the start of study treatment to completion of 48 cycles (each cycle is 28 days) or the earlier of the first documentation of disease progression or death from any cause

Eligibility
Key inclusion criteria
1. Men and women =18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place)
2. Diagnosis of CLL that meets all published diagnostic criteria (Hallek et al. 2018):

1. Monoclonal B-cells (either kappa or lambda light chain restricted) that are clonally co-expressing =1 B-cell marker (CD19, CD20, and CD23) and CD5 during screening
2. Prolymphocytes may comprise <55% of blood lymphocytes during screening
3. Presence of =5 × 10^9 B lymphocytes/L (5000/µL) in the peripheral blood (at any point since the initial diagnosis)
3. Active disease per at least 1 of the following iwCLL 2018 criteria

1. Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (hemoglobin <10 g/dL) and/or thrombocytopenia (platelets <100,000/µL).
2. Massive (i.e., =6 cm below the left costal margin), progressive, or symptomatic splenomegaly.
3. Massive nodes (i.e., =10 cm in the longest diameter), progressive, or symptomatic lymphadenopathy
4. Progressive lymphocytosis with an increase of >50% over a 2-month period or a lymphocyte doubling time (LDT) of <6 months. LDT may be obtained by linear regression extrapolation of absolute lymphocyte count obtained at intervals of 2 weeks over an observation period of 2 to 3 months. In participants with initial blood lymphocyte counts of <30x10^9/L (30,000/µL), LDT should not be used as a single parameter to define indication for treatment. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (e.g., infections) should be excluded.
5. Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy
6. B-symptoms documented in the participant's chart with supportive objective measures, as appropriate, defined as =1 of the following disease-related symptoms or signs: o- Unintentional weight loss =10% within the previous 6 months before screening o- Significant fatigue (Eastern Cooperative Oncology Group [ECOG] performance status =2; inability to work or perform usual activities) o- Fevers higher than 100.5°F or 38.0°C for =2 weeks o- Night sweats for =1 month before screening without evidence of infection
4. Must meet one of the following criteria:

a. Have received no prior therapy for treatment of CLL and meets one of the following criteria (for this study, participants in the UK will be enrolled ONLY in the R/R or the prior ibrutinib cohort): i. A score of >6 on the Cumulative Illness Rating Scale (CIRS) ii. Creatinine clearance of 30 to 69 mL/min using the Cockcroft-Gault equation b. Have previously received therapy for CLL and have either refractory or relapsed CLL c. Have received prior ibrutinib therapy (i.e., defined as a participant who discontinued a ibrutinib for any reason prior to disease progression) for CLL (participants in the US will not be enrolled into the prior ibrutinib therapy cohort)
5. ECOG performance status of =2
6. Female participants of childbearing potential (i.e., not surgically sterile or postmenopausal) who are sexually active with a non-sterilized male partner must use =1 highly effective method of contraception from the time of screening and must agree to continue using such precautions for 2 days after the last dose of study intervention. Contraception measures and restrictions on sperm donation are not required for male participants.
7. Fluorescence in situ hybridization (FISH) for which the next-generation sequencing (NGS) method is preferred) within 60 days during screening up to before the first dose reflecting the presence or absence of del(17p), del(13q), del(11q), and trisomy of chromosome 12 along with the percentage of cells with the deletion, along with TP53 sequencing. Participants must also have molecular analysis to detect IGHV mutation status (NGS is the preferred method) at screening if not done at any time point before that since diagnosis.
8. Each participant (or legally authorized representative if allowed per local regulations) must be willing and able to adhere to the study visit schedule, understand and comply with other protocol requirements, and provide written informed consent and authorization to use protected health information.
Minimum age
18 Years
Maximum age
130 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Participants who have had disease progression while on a BTKi for any malignant or nonmalignant condition
2. Prior malignancy (other than CLL), except for adequately treated basal cell or squamous cell skin cancer, in situ cancer, early stage prostate cancer, or other cancer from which the participant has been disease-free for =2 years
3. History of confirmed progressive multifocal leukoencephalopathy
4. Significant cardiovascular disease such as symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months before screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or corrected QT interval using Fridericia's formula (QTcF) >480 msec at screening. Note: Participants with rate-controlled, asymptomatic atrial fibrillation are allowed to enroll in the study (For prior ibrutinib therapy cohort only, except in Finland and the Republic of South Korea, where this is applicable to all 3 cohorts; also, the prior ibrutinib therapy cohort will not be enrolled in the US).
5. Malabsorption syndrome, disease significantly affecting gastrointestinal (GI) function, resection of the stomach, extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
6. Evidence of active Richter's transformation. If Richter's transformation is suspected (i.e., lactate dehydrogenase [LDH] increased, asymmetric fast lymph node growth or clinical suspicion), it should be ruled out with positron emission tomographycomputed tomography (PET-CT) and/or biopsy according to guidelines.
7. Central nervous system (CNS) involvement by CLL.
8. Known history of human immunodeficiency virus, serologic status reflecting active hepatitis B virus or hepatitis C virus infection, any uncontrolled active systemic infection along with participants who are on ongoing anti-infective treatment and participants who have received vaccination with a live attenuated vaccine within 4 weeks before the first dose of study intervention.

1. Participants who are hepatitis B core antibody (anti-HBc) positive and who are hepatitis B surface antibody (anti-HBs) negative will need to have a negative hepatitis B virus PCR result before enrollment. Those who are hepatitis B surface antigen (HBsAg) positive or hepatitis B virus PCR positive will be excluded.
2. Participants who are hepatitis C virus antibody positive will need to have a negative hepatitis C virus PCR result before enroll.lment. Those who are hepatitis C virus PCR positive will be excluded
9. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura defined as declining hemoglobin or platelet count secondary to autoimmune destruction within the screening period or requirement for high doses of steroids (>20 mg daily of prednisone or equivalent for longer than 2 weeks).
10. History of stroke or intracranial hemorrhage within 6 months before the first dose of study intervention.
11. History of bleeding diathesis (e.g., hemophilia or von Willebrand disease)
12. Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening.
13. Major surgical procedure within 4 weeks before first dose of study intervention. Note: Participants who have had major surgery must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study intervention.
14. Requires treatment with proton-pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Participants receiving proton-pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrollment in this study.
15. All participants requiring or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon) within 7 days before first dose of study intervention. Based on the known metabolic/transport pathways involved in the disposition of acalabrutinib and the commonly known novel oral anticoagulants (eg, apixaban, rivaroxaban, and edoxaban), no clinically relevant interaction is expected following coadministration of these agents.
16. Absolute neutrophil count (ANC) <0.50 x 10^9/L or platelet count <30 x 10^9/L, unless proven due to CLL and raised above the limits by granulocyte colony-stimulating factor (G-CSF) therapy and/or pooled platelet transfusion
17. Total bilirubin >3.0x upper limit of normal (ULN); or aspartate aminotransferase or alanine aminotransferase >3.0x ULN. Exception will be for Gilbert syndrome; if an investigator feels that a participant's total bilirubin is elevated secondary to Gilbert's, the participant must have a documented unconjugated bilirubin being >80% of the total bilirubin number. The investigator must also document that hemolysis has been ruled out along with (near)-normal lactate dehydrogenase and haptoglobin
18. Estimated creatinine clearance of <30 mL/min, calculated using the formula of Cockcroft and Gault or by direct assessment (i.e., creatinine clearance or ethylene diamine tetra-acetic acid (EDTA) clearance measurement)
19. Breastfeeding or pregnant
20. Received any chemotherapy, external beam radiation, investigational drug, or any other anti-CLL therapy within 30 days before first dose of study intervention
21. Concurrent participation in another therapeutic clinical study
22. History of or ongoing interstitial lung disease
23. Requiring long-term (> 1 week) treatment with a strong cytochrome CYP3A inhibitor/inducer. In addition, the use of strong or moderate CYP3A inhibitors or inducers within 7 days of the first dose of study intervention is prohibited.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
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
17/09/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/09/2025
Actual
Sample size
Target
Accrual to date
Final
552
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Adelaide
Recruitment hospital [2] 0 0
Research Site - Bedford Park
Recruitment hospital [3] 0 0
Research Site - Clayton
Recruitment hospital [4] 0 0
Research Site - Fitzroy
Recruitment hospital [5] 0 0
Research Site - Nedlands
Recruitment hospital [6] 0 0
Research Site - South Brisbane
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
5042 - Bedford Park
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3065 - Fitzroy
Recruitment postcode(s) [5] 0 0
6009 - Nedlands
Recruitment postcode(s) [6] 0 0
4101 - South Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Louisiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Minnesota
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
Brazil
State/province [13] 0 0
Belo Horizonte
Country [14] 0 0
Brazil
State/province [14] 0 0
Curitiba
Country [15] 0 0
Brazil
State/province [15] 0 0
Goiania
Country [16] 0 0
Brazil
State/province [16] 0 0
Porto Alegre
Country [17] 0 0
Brazil
State/province [17] 0 0
Ribeirão Preto
Country [18] 0 0
Brazil
State/province [18] 0 0
Sao Paulo
Country [19] 0 0
Brazil
State/province [19] 0 0
São Paulo
Country [20] 0 0
Canada
State/province [20] 0 0
Alberta
Country [21] 0 0
Canada
State/province [21] 0 0
British Columbia
Country [22] 0 0
Canada
State/province [22] 0 0
Manitoba
Country [23] 0 0
Canada
State/province [23] 0 0
Nova Scotia
Country [24] 0 0
Canada
State/province [24] 0 0
Ontario
Country [25] 0 0
Denmark
State/province [25] 0 0
Aalborg
Country [26] 0 0
Denmark
State/province [26] 0 0
Aarhus
Country [27] 0 0
Denmark
State/province [27] 0 0
Herlev
Country [28] 0 0
Denmark
State/province [28] 0 0
København Ø
Country [29] 0 0
Denmark
State/province [29] 0 0
Odense
Country [30] 0 0
Denmark
State/province [30] 0 0
Roskilde
Country [31] 0 0
Finland
State/province [31] 0 0
Hus
Country [32] 0 0
Finland
State/province [32] 0 0
Kuopio
Country [33] 0 0
Finland
State/province [33] 0 0
Tampere
Country [34] 0 0
France
State/province [34] 0 0
Bordeaux
Country [35] 0 0
France
State/province [35] 0 0
Brest
Country [36] 0 0
France
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Limoges
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France
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Reims
Country [38] 0 0
France
State/province [38] 0 0
Tours
Country [39] 0 0
France
State/province [39] 0 0
Vandoeuvre-Les-Nancy
Country [40] 0 0
Germany
State/province [40] 0 0
Bayern
Country [41] 0 0
Germany
State/province [41] 0 0
Essen
Country [42] 0 0
Germany
State/province [42] 0 0
Homburg
Country [43] 0 0
Germany
State/province [43] 0 0
Porta Westfalica
Country [44] 0 0
Germany
State/province [44] 0 0
Schwäbisch Hall
Country [45] 0 0
Italy
State/province [45] 0 0
Catanzaro
Country [46] 0 0
Italy
State/province [46] 0 0
Milano
Country [47] 0 0
Italy
State/province [47] 0 0
Roma
Country [48] 0 0
Italy
State/province [48] 0 0
Siena
Country [49] 0 0
Korea, Republic of
State/province [49] 0 0
Busan
Country [50] 0 0
Korea, Republic of
State/province [50] 0 0
Seoul
Country [51] 0 0
Korea, Republic of
State/province [51] 0 0
Ulsan
Country [52] 0 0
Netherlands
State/province [52] 0 0
Arnhem
Country [53] 0 0
Netherlands
State/province [53] 0 0
Dordrecht
Country [54] 0 0
Netherlands
State/province [54] 0 0
Utrecht
Country [55] 0 0
Norway
State/province [55] 0 0
Bergen
Country [56] 0 0
Norway
State/province [56] 0 0
Oslo
Country [57] 0 0
Norway
State/province [57] 0 0
Trondheim
Country [58] 0 0
Russian Federation
State/province [58] 0 0
Moscow
Country [59] 0 0
Russian Federation
State/province [59] 0 0
Nizhny Novgorod
Country [60] 0 0
Russian Federation
State/province [60] 0 0
Petrozavodsk
Country [61] 0 0
Russian Federation
State/province [61] 0 0
Saint Petersburg
Country [62] 0 0
Russian Federation
State/province [62] 0 0
Saint-Petersburg
Country [63] 0 0
Russian Federation
State/province [63] 0 0
Smolensk
Country [64] 0 0
Russian Federation
State/province [64] 0 0
St. Petersburg
Country [65] 0 0
Russian Federation
State/province [65] 0 0
Syktyvkar
Country [66] 0 0
Spain
State/province [66] 0 0
Barcelona
Country [67] 0 0
Spain
State/province [67] 0 0
Madrid
Country [68] 0 0
Spain
State/province [68] 0 0
Marbella
Country [69] 0 0
Spain
State/province [69] 0 0
Ourense
Country [70] 0 0
Spain
State/province [70] 0 0
Oviedo
Country [71] 0 0
Spain
State/province [71] 0 0
Vitoria
Country [72] 0 0
Spain
State/province [72] 0 0
Zaragoza
Country [73] 0 0
Sweden
State/province [73] 0 0
Luleå
Country [74] 0 0
Sweden
State/province [74] 0 0
Lund
Country [75] 0 0
Sweden
State/province [75] 0 0
Uppsala
Country [76] 0 0
Taiwan
State/province [76] 0 0
Taichung
Country [77] 0 0
Taiwan
State/province [77] 0 0
Tainan
Country [78] 0 0
Taiwan
State/province [78] 0 0
Taipei
Country [79] 0 0
United Kingdom
State/province [79] 0 0
Liverpool
Country [80] 0 0
United Kingdom
State/province [80] 0 0
Newmarket

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Parexel
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Adel Habib, MD
Address 0 0
AstraZeneca
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.

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 de-identified 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?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04008706