A Study of Acalabrutinib vs Investigator's Choice of Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in R/R CLL
A Randomized, Multicenter, Open-Label, Phase 3 Study of Acalabrutinib (ACP-196) Versus Investigator's Choice of Either Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Subjects With R/R Chronic Lymphocytic Leukemia
2 other identifiers
interventional
310
24 countries
146
Brief Summary
This study is designed to evaluate the efficacy of acalabrutinib compared with rituximab in combination with idelalisib or bendamustine in previously treated subjects with chronic lymphocytic leukemia (CLL).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Feb 2017
Longer than P75 for phase_3
146 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 18, 2016
CompletedFirst Posted
Study publicly available on registry
November 22, 2016
CompletedStudy Start
First participant enrolled
February 2, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 3, 2021
CompletedResults Posted
Study results publicly available
June 29, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2027
ExpectedFebruary 6, 2026
January 1, 2026
4.6 years
November 18, 2016
September 2, 2022
January 20, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression-free Survival (PFS) Per Independent Review Committee (IRC) Assessment
To evaluate the efficacy of acalabrutinib monotherapy (Arm A) compared with idelalisib/rituximab or bendamustine/rituximab (Arm B) based on Independent Review Committee (IRC) assessment of progression-free survival (PFS) per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria (Hallek 2008) with incorporation of the clarification for treatment-related lymphocytosis (Cheson 2012) hereafter referred to as IWCLL 2008 criteria in subjects with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL). As planned and reported in the interim clinical study report (dated 17 July 2019), because the study did cross the boundary at interim analysis. IRC assessments were discontinued after the interim analysis. All IRC-related efficacy analyses in this clinical study report were based on the interim analysis data cutoff date of 15 January 2019. All other efficacy analyses were based on the final analysis data cutoff date of 03 September 2021.
IRC assessments from randomization date until disease progression or death or IRC discontinuation on 15Jan2019 (as IA per this data cutoff showed crossing superiority boundary) whichever came first, up to 22 months of follow-up
Secondary Outcomes (7)
Progression-free Survival (PFS) Per Investigator Assessment
From randomization date to date of disease progression or death due to any cause or data cutoff date on 03Sep2021, whichever came first, regardless of use of subsequent anticancer therapy, until 53 months of follow-up.
IRC-assessed Overall Response Rate (ORR) Per IWCLL 2008 Criteria Based on Data Cutoff 15 January 2019 From Interim Analysis
IRC assessments from randomization date until disease progression or death or IRC discontinuation on 15Jan2019 (as IA per this data cutoff showed crossing superiority boundary) whichever came first, up to 22 months of follow-up
Investigator Assessed Overall Response Rate (ORR) Per IWCLL 2008 Criteria Based on Data Cutoff 03 September 2021
Investigator assessments were done from randomization date until date of death or date of exit from study or data cut off date on 03Sep2021, whichever came first, up to 53 months of follow-up.
Overall Survival (OS)
From randomization date to date of death due to any cause, or date of study discontinuation, or date of data cutoff on 03Sep2021, whichever came first until 54 months of follow-up.
Duration of Response (DOR) Per Independent Review Committee (IRC) Assessment Based on 15 January 2019 Data Cutoff From Interim Analysis.
IRC assessments from randomization date until disease progression or death or IRC discontinuation on 15Jan2019 (as IA per this data cutoff showed crossing superiority boundary) whichever came first, up to 22 months of follow-up
- +2 more secondary outcomes
Study Arms (2)
Acalabrutinib (ACP-196)
EXPERIMENTALAcalabrutinib (ACP-196) Monotherapy
Rituximab Plus Idelalisib or Bendamustine
ACTIVE COMPARATORInvestigator's Choice of Rituximab Plus Idelalisib or Bendamustine
Interventions
Rituximab in combination with idelalisib or bendamustine
Eligibility Criteria
You may qualify if:
- Men and women ≥ 18 years of age.
- ECOG performance status of 0 to 2.
- Diagnosis of CLL that meets published diagnostic criteria (Hallek 2008):
- Monoclonal B-cells (either kappa or lambda light chain restricted) that are clonally co-expressing ≥ 1 B-cell marker (CD19, CD20, or CD23) and CD5.
- Prolymphocytes may comprise ≤ 55% of blood lymphocytes.
- Presence of ≥ 5 x 10\^9 B lymphocytes/L (5000/μL) in the peripheral blood (at any point since initial diagnosis).
- Must have documented CD20-positive CLL.
- Active disease meeting ≥ 1 of the following IWCLL 2008 criteria for requiring treatment:
- 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).
- Massive (i.e., ≥ 6 cm below the left costal margin), progressive, or symptomatic splenomegaly.
- Massive nodes (i.e., ≥ 10 cm in the longest diameter), progressive, or symptomatic lymphadenopathy.
- Progressive lymphocytosis with an increase of \> 50% over a 2-month period or a LDT of \< 6 months. LDT may be obtained by linear regression extrapolation of ALC obtained at intervals of 2 weeks over an observation period of 2 to 3 months. In subjects with initial blood lymphocyte counts of \< 30 x 10\^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.
- Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy.
- Constitutional symptoms documented in the subject's chart with supportive objective measures, as appropriate, defined as ≥ 1 of the following disease-related symptoms or signs:
- i. Unintentional weight loss ≥ 10% within the previous 6 months before screening.
- +15 more criteria
You may not qualify if:
- Known CNS lymphoma or leukemia.
- Known prolymphocytic leukemia or history of, or currently suspected, Richter's syndrome.
- Uncontrolled AIHA or ITP 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).
- Prior exposure to a BCL-2 inhibitor (e.g., venetoclax/ABT-199) or a BCR inhibitor (e.g., BTK inhibitors or PI3K inhibitors). Prior bendamustine is allowed if Investigator's choice for treatment in Arm B is idelalisib with rituximab. Bendamustine retreatment is allowed if the prior response to bendamustine lasted \> 24 months.
- Received any chemotherapy, external beam radiation therapy, anticancer antibodies, or investigational drug within 30 days before first dose of study drug.
- Corticosteroid use \> 20 mg daily prednisone equivalent within 1 week before first dose of study drug, except as indicated for other medical conditions such as inhaled steroid for asthma, topical steroid use, or as premedication for administration of study drug or contrast. For example, subjects requiring steroids at daily doses \> 20 mg prednisone equivalent systemic exposure daily, or those who are administered steroids for leukemia control or white blood cell count lowering are excluded.
- Prior radio- or toxin-conjugated antibody therapy.
- Prior allogeneic stem cell transplant or prior autologous transplant within 6 months of first dose of study drug(s) or presence of graft-vs-host disease or receiving treatment for graft-vs-host disease.
- Major surgical procedure within 30 days of first dose of study drug. Note: If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug.
- History of prior malignancy except for the following:
- Malignancy treated with curative intent and with no evidence of active disease present for more than 2 years before screening and felt to be at low risk for recurrence by treating physician.
- Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled nonmelanomatous skin cancer.
- Adequately treated carcinoma in situ without current evidence of disease.
- Significant cardiovascular disease such as uncontrolled or untreated symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or QTc \> 480 msec (calculated using Fridericia's formula: QT/RR\^0.33) at screening. Exception: Subjects with controlled, asymptomatic atrial fibrillation during screening are allowed to enroll on study.
- Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach, or extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
- +19 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Acerta Pharma BVlead
Study Sites (157)
Research Site
Chandler, Arizona, 85224, United States
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Oxnard, California, 93030, United States
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Athens, Georgia, 30607, United States
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Joliet, Illinois, 60435, United States
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Cedar Rapids, Iowa, 52403, United States
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Mount Sterling, Kentucky, 40353, United States
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Saint Cloud, Minnesota, 56303, United States
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Lincoln, Nebraska, 68506, United States
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Brick, New Jersey, 08724, United States
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Nyack, New York, 10960, United States
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Canton, Ohio, 44719, United States
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Fort Sam Houston, Texas, 78234, United States
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Round Rock, Texas, 78665, United States
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Adelaide, 5000, Australia
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Box Hill, 3128, Australia
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Frankston, 3199, Australia
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Geelong, 3220, Australia
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Gosford, 2250, Australia
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Hobart, 7000, Australia
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Kogarah, 2217, Australia
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Murdoch, 6150, Australia
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Nedlands, 6009, Australia
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South Brisbane, 4101, Australia
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Woodville, 5011, Australia
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Linz, 4010, Austria
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Salzburg, 5020, Austria
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Vienna, 1130, Austria
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Vienna, 1160, Austria
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Wels, 4600, Austria
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Antwerp, 2060, Belgium
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Ghent, 9000, Belgium
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Roeselare, 8900, Belgium
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Yvoir, 5530, Belgium
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Pleven, 5800, Bulgaria
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Plovdiv, 4002, Bulgaria
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Stara Zagora, 6000, Bulgaria
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Vratsa, 3000, Bulgaria
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Barrie, Ontario, L4M 6M2, Canada
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Calgary, T2N 2T9, Canada
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Montreal, H3T 1E2, Canada
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Ottawa, K1H 8L6, Canada
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Regina, S4T 7T1, Canada
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Saint John, E2L 4L2, Canada
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Toronto, M4N 3M5, Canada
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Toronto, M5G 2M9, Canada
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Zadar, 23 000, Croatia
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Zagreb, 10 000, Croatia
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Brno, 625 00, Czechia
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NovĂ½ Hradec KrĂ¡lovĂ©, 500 05, Czechia
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Olomouc, 779 00, Czechia
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Ostrava Poruba, 708 52, Czechia
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Plzen - Lochotin, 304 60, Czechia
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Prague, 100 34, Czechia
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Bordeaux, 33076, FR, France
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Brest, 29609, France
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Montpellier, 34295, France
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Nantes, 44093, France
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Paris, 75010, France
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Paris, 75651, France
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Perpignan, 66000, France
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Provence Alpes Cote D'Azur, 13273, France
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Rennes, 35000, France
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Rouen, 76038, France
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Aschaffenburg, 63739, Germany
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Dresden, 1307, Germany
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Mutlangen, 73557, Germany
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MĂ¼nchen, 81377, Germany
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Ulm, 89081, Germany
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Hong Kong, 150001, Hong Kong
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Pok Fu Lam, Hong Kong
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Budapest, 1122, Hungary
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Debrecen, 4032, Hungary
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Gyula, 5700, Hungary
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KaposvĂ¡r, 7400, Hungary
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Ashkelon, 7830604, Israel
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Haifa, 34362, Israel
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Jerusalem, 9112001, Israel
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Kfar Saba, 4428164, Israel
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Nahariya, 22100, Israel
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Petah Tikvah, 49102, Israel
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Aviano, 33081, Italy
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Bergamo, 24127, Italy
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Brescia, 25123, Italy
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Florence, 50134, Italy
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Genova, 16126, Italy
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Genova, 16132, Italy
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Meldola, 47014, Italy
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Milan, 20132, Italy
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Milan, 20162, Italy
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Modena, 41100, Italy
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Addington, 8011, New Zealand
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Dunedin, 9016, New Zealand
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Palmerston North, 4442, New Zealand
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Tauranga, 3112, New Zealand
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Bialystok, 15-276, Poland
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Bydgoszcz, 85-168, Poland
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Gdansk, 80-129, Poland
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Krakow, 30-727, Poland
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Lodz, 93-510, Poland
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Lublin, 20-081, Poland
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Woj. Podkarpackie, 36-200, Poland
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Novosibirsk, 630087, Russia
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Obninsk, 249031, Russia
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Penza, 440008, Russia
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Ryazan, 390000, Russia
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Saint Petersburg, 194044, Russia
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Saint Petersburg, 197341, Russia
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Sochi, Unk, Russia
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Tula, 300053, Russia
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Volgograd, Unk, Russia
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Yaroslavl, 150023, Russia
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Yekaterinburg, 620072, Russia
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SGP, 169608, Singapore
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SGP, 188770, Singapore
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SGP, 217562, Singapore
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Bratislava, 833 10, Slovakia
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Košice, 040 01, Slovakia
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Busan, 49241, South Korea
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Daegu, 41944, South Korea
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Donggu, 44033, South Korea
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Gyeonggi-do, 13620, South Korea
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Incheon, UNK, South Korea
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Jeonju, 54907, South Korea
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Seoul, 3080, South Korea
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Seoul, 3722, South Korea
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Badalona, 8916, Spain
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Madrid, 28006, Spain
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Madrid, 28009, Spain
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Madrid, 28031, Spain
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Madrid, 28033, Spain
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Madrid, 28041, Spain
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Majadahonda, 28222, Spain
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Salamanca, 37007, Spain
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Santander, 39008, Spain
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Valencia, 46026, Spain
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Gothenburg, 413 46, Sweden
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LuleĂ¥, 97180, Sweden
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Stockholm, 171 76, Sweden
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Hualien City, 970, Taiwan
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Tainan, 70403, Taiwan
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Taipei, 100, Taiwan
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Cherkasy, 18009, Ukraine
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Dnipropetrovsk, 49102, Ukraine
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Ivano-Frankivsk, Ukraine
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Khmelnytsky, 29000, Ukraine
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Kyiv, 03022, Ukraine
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Kyiv, Ukraine
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Zhytomyr, 10002, Ukraine
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Birmingham, B9 5SS, United Kingdom
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Cambridge, CB2 0QQ, United Kingdom
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Canterbury, CT1 3NG, United Kingdom
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Leicester, LE1 7RH, United Kingdom
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London, SE5 9RS, United Kingdom
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Maidstone, ME16 9QQ, United Kingdom
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Manchester, M20 4BX, United Kingdom
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Southampton, SO16 6YD, United Kingdom
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Wolverhampton, WV10 0QP, United Kingdom
Related Publications (2)
Eek D, Ivanescu C, Corredoira L, Meyers O, Cella D. Content validity and psychometric evaluation of the Functional Assessment of Chronic Illness Therapy-Fatigue scale in patients with chronic lymphocytic leukemia. J Patient Rep Outcomes. 2021 Mar 11;5(1):27. doi: 10.1186/s41687-021-00294-1.
PMID: 33709202DERIVEDGhia P, Pluta A, Wach M, Lysak D, Kozak T, Simkovic M, Kaplan P, Kraychok I, Illes A, de la Serna J, Dolan S, Campbell P, Musuraca G, Jacob A, Avery E, Lee JH, Liang W, Patel P, Quah C, Jurczak W. ASCEND: Phase III, Randomized Trial of Acalabrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia. J Clin Oncol. 2020 Sep 1;38(25):2849-2861. doi: 10.1200/JCO.19.03355. Epub 2020 May 27.
PMID: 32459600DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Astrazeneca Clinical Trial
Study Officials
- STUDY DIRECTOR
Acerta Clinical Trials
1-888-292-9613; acertamc@dlss.com
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 18, 2016
First Posted
November 22, 2016
Study Start
February 2, 2017
Primary Completion
September 3, 2021
Study Completion (Estimated)
October 1, 2027
Last Updated
February 6, 2026
Results First Posted
June 29, 2023
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- 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.
- Access Criteria
- 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.
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.