Acalabrutinib, Obinutuzumab and Chlorambucil in Treatment naïve CLL
ElevateTN
A Randomized, Multicenter, Open-Label, 3 Arm Phase 3 Study of Obinutuzumab in Combination With Chlorambucil, Acalabrutinib (ACP-196) in Combination With Obinutuzumab, and Acalabrutinib Monotherapy in Subjects With Previously Untreated CLL
3 other identifiers
interventional
535
18 countries
155
Brief Summary
This Primary objective is evaluating the efficacy of obinutuzumab in combination with chlorambucil (Arm A) compared with acalabrutinib in combination with obinutuzumab (Arm B) for the treatment of previously untreated chronic lymphocytic leukemia (CLL). Secondary objectives: 1) To evaluate the efficacy of obinutuzumab in combination with chlorambucil (Arm A) versus acalabrutinib monotherapy (Arm C) based on IRC assessment of PFS per IWCLL 2008 criteria. 2)To compare obinutuzumab plus chlorambucil (Arm A) versus acalabrutinib plus obinutuzumab (Arm B) and obinutuzumab plus chlorambucil (Arm A) versus acalabrutinib monotherapy (Arm C) in terms of: IRC-assessed objective response rate (ORR); Tine to next treatment (TTNT); Overall Survival (OS)
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jun 2015
Longer than P75 for phase_3
155 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
June 12, 2015
CompletedFirst Posted
Study publicly available on registry
June 19, 2015
CompletedStudy Start
First participant enrolled
June 26, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 8, 2019
CompletedResults Posted
Study results publicly available
January 10, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
September 30, 2025
CompletedAugust 27, 2025
August 1, 2025
3.6 years
June 12, 2015
February 28, 2020
August 26, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Progression-free Survival by IRC (Independent Review Committee) Assessment in Arm A Compared to Arm B
To evaluate the efficacy of obinutuzumab in combination with chlorambucil (Arm A) compared with acalabrutinib in combination with obinutuzumab (Arm B) based on IRC assessment of progression-free survival (PFS) per International Workshop on Chronic Lymphocytic Leukemia criteria (IWCLL; Hallek et al. 2008) with incorporation of the clarification for treatment-related lymphocytosis (Cheson et al. 2012), hereafter referred to as IWCLL 2008 criteria, in subjects with previously untreated CLL. PFS, defined as the time from date of randomization to the date of first IRC-assessed disease progression or death due to any cause, whichever comes first.
IRC assessments were done from randomization date until disease progression or death or IRC discontinuation date on 08Feb2019 (as the IA based on this data cutoff date showed the study crossing superiority boundary) whichever comes first up to 40 months.
Secondary Outcomes (4)
Progression-free Survival by IRC Assessment Arm A Versus Arm C
IRC assessments were done from randomization date until disease progression or death or IRC discontinuation date on 08Feb2019 (as the IA based on this data cutoff date showed the study crossing superiority boundary) whichever comes first up to 40 months.
IRC-assessed Objective Response Rate (ORR) in Arm A Versus Arm B and Arm A Versus Arm C
IRC assessments were done from randomization date until disease progression or death or IRC discontinuation date on 08Feb2019 (as the IA based on this data cutoff date showed the study crossing superiority boundary) whichever comes first up to 40 months.
Time to Next Treatment (TTNT) in Arm A Versus Arm B and Arm A Versus Arm C
From randomization date to start of non-protocol specified subsequent anticancer therapy for CLL or death due to any cause, whichever came first assessed up to 40 months of follow-up.
Overall Survival (OS) in Arm A Versus Arm B and Arm A Versus Arm C
From randomization date until death, withdrawal by subject, lost to follow-up, or by analysis data cut off date on 08Feb2019 whichever comes first up to 40 months of follow-up.
Study Arms (3)
Arm A - Obinutuzumab in Combination with Chlorambucil
ACTIVE COMPARATORObinutuzumab IV infusions will be administered over a total of 6 treatment cycles starting at Cycle 1 Day 1. Chlorambucil will be orally administered on Days 1 and 15 of Cycles 1 through 6.
Arm B - Acalabrutinib in Combination with Obinutuzumab
EXPERIMENTALObinutuzumab IV infusions will be administered over a total of 6 treatment cycles starting at Cycle 2 Day 1. Acalabrutinib (ACP-196) will be orally administered starting on Cycle 1 Day 1. Daily administration of Acalabrutinib (ACP-196) will continue until disease progression or unacceptable toxicity.
Arm C - Acalabrutinib Monotherapy
EXPERIMENTALAcalabrutinib (ACP-196) will be orally administered on Cycle 1 Day 1 until disease progression or unacceptable toxicity.
Interventions
Eligibility Criteria
You may qualify if:
- Men and women:
- a. ≥ 65 years of age OR b. \> 18 and \< 65 years of age, provided that they meet at least one of the following criteria: i. Creatinine clearance 30 to 69 mL/min using the Cockcroft-Gault equation ii. A score higher than 6 on the CIRS-G (Appendix L).
- ECOG performance status of 0, 1, or 2.
- Diagnosis of CD20+ 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 109 B lymphocytes/L (5000 μL) in the peripheral blood (at any point since diagnosis)
- 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 109/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:
- Any prior systemic treatment for CLL (note: Prior localized radiotherapy is allowed).
- Known CNS lymphoma or leukemia.
- Known prolymphocytic leukemia or history of, or currently suspected, Richter's syndrome.
- Missing or incomplete documentation of FISH results reflecting the presence or absence of 17p del and the percentage of cells with the deletion in subject records before randomization.
- 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 daily or equivalent).
- Corticosteroid use \> 20 mg 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 WBC count lowering are excluded.
- Major surgery within 4 weeks before 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 3 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 non-melanomatous skin cancer.
- Adequately treated cervical carcinoma in situ without current evidence of disease.
- Significant cardiovascular disease such as uncontrolled or 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 at screening.
- Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or gastric bypass, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
- Uncontrolled active systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment) or ongoing intravenous anti-infective treatment.
- Known history of infection with HIV. 13. Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Acerta Pharma BVlead
Study Sites (155)
Research Site
Goodyear, Arizona, 85395, United States
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Phoenix, Arizona, 85016, United States
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Anaheim, California, 92801, United States
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Los Angeles, California, 90017, United States
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Los Angeles, California, 90033, United States
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Los Angeles, California, 90095, United States
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Oxnard, California, 93030, United States
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Palo Alto, California, 94304, United States
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Aurora, Colorado, 80045, United States
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Lone Tree, Colorado, 80124, United States
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Washington D.C., District of Columbia, 20007, United States
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Fort Myers, Florida, 33901-8101, United States
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Jacksonville, Florida, 32224, United States
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Tallahassee, Florida, 32308-5304, United States
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Tallahassee, Florida, 32308, United States
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Tampa, Florida, 33612, United States
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Niles, Illinois, 60714, United States
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Lafayette, Indiana, 47904, United States
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Wichita, Kansas, 67214, United States
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Louisville, Kentucky, 40207, United States
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New Orleans, Louisiana, 70112, United States
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COL, Maryland, 21044, United States
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Rochester, Minnesota, 55905, United States
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Saint Cloud, Minnesota, 56303, United States
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Billings, Montana, 59102, United States
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Brick, New Jersey, 08724, United States
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Hackensack, New Jersey, ?07601, United States
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Lake Success, New York, 11042, United States
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New York, New York, 10029, United States
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Blue Ash, Ohio, 45242, United States
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Canton, Ohio, 44719, United States
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Columbus, Ohio, 43210, United States
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Nashville, Tennessee, 37203, United States
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Austin, Texas, 78705, United States
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Bedford, Texas, 76022, United States
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Dallas, Texas, 75230, United States
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Fort Sam Houston, Texas, 78234, United States
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Houston, Texas, 77030, United States
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New Braunfels, Texas, 78130, United States
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Round Rock, Texas, 76508, United States
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San Antonio, Texas, 78258, United States
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Texas City, Texas, 77591, United States
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Tyler, Texas, 75702, United States
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Salt Lake City, Utah, 84112, United States
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Roanoke, Virginia, 24014, United States
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Seattle, Washington, 98109, United States
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Seattle, Washington, 98122, United States
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Spokane, Washington, 99208, United States
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Tacoma, Washington, 98405, United States
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Yakima, Washington, 98902, United States
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Northwest WA, Wisconsin, 20007, United States
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Darlinghurst, 2010, Australia
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Frankston, 3199, Australia
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Geelong, 3220, Australia
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South Brisbane, QLD 4101, Australia
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Waratah NSW, 2298, Australia
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Wollongong, 2500, Australia
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Woodville, 5011, Australia
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Bruges, 8000, Belgium
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Brussels, 1090, Belgium
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Brussels, 1200, Belgium
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Ghent, 9000, Belgium
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Kortrijk, 8500, Belgium
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Leuven, 3000, Belgium
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Roeselare, 8900, Belgium
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Wilrijk, 2610, Belgium
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Yvoir, 5530, Belgium
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Barretos, 14784-400, Brazil
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Florianópolis, 88034-000, Brazil
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Passo Fundo, 99010-260, Brazil
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Porto Alegre, 90035-903, Brazil
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Porto Alegre, 90470-340, Brazil
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São Paulo, 155, Brazil
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Vancouver, British Columbia, V5Z 4E6, Canada
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Halifax, Nova Scotia, B3H2Y9, Canada
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Québec, G1J 1Z4, Canada
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Saint John, E2L 4L2, Canada
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Winnipeg, R3E 0V9, Canada
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Santiago, 8380455, Chile
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Temuco, 4810469, Chile
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Medellín, 050034, Colombia
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Montería, 110221, Colombia
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Bobigny, 93000, France
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Dijon, 21000, France
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Pierre-Bénite, 69310, France
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Strasbourg, 67098, France
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Villejuif, 94800, France
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Aschaffenburg, 63739, Germany
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Bielefeld, 33604, Germany
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Erlangen, 91052, Germany
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Heilbronn, 74078, Germany
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Warzburg, 97080, Germany
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Budapest, 1085, Hungary
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Budapest, 1122, Hungary
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Debrecen, 4032, Hungary
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Kaposvár, 7400, Hungary
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Szolnok, 5004, Hungary
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Ashkelon, 7830604, Israel
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Beersheba, 84101, Israel
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Haifa, 31000, Israel
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Haifa, 31096, Israel
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Haifa, 34362, Israel
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Jerusalem, 9103102, Israel
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Nahariya, 22100, Israel
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Petah Tikvah, 49100, Israel
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Petah Tikvah, 49102, Israel
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Rehovot, 76100, Israel
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Tel Aviv, 64239, Israel
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Tel Litwinsky, 52621, Israel
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Tiberias, 15208, Israel
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Alessandria, 15100, Italy
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Aviano, 33081, Italy
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Brescia, 25123, Italy
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Florence, 50134, Italy
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Meldola, 47014, Italy
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Milan, 20132, Italy
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Parma, Italy
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Ravenna, 48121, Italy
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Rimini, 47900, Italy
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Rome, 168, Italy
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Rozzano, 20089, Italy
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Kaunas, LT-50009, Lithuania
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Klaipėda, LT-92288, Lithuania
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Vilnius, LT-08661, Lithuania
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Auckland, ?0620, New Zealand
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Otahuhu, 2025, New Zealand
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Tauranga, 3112, New Zealand
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Bydgoszcz, 85-168, Poland
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Gdansk, 80-129, Poland
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Gdynia, 81-519, 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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Olsztyn, 10-228, Poland
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Opole, 46-020, Poland
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Słupsk, 76-200, Poland
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Barcelona, ?08041, Spain
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Madrid, 28006, Spain
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Madrid, 28031, Spain
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Madrid, 28041, Spain
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Majadahonda, 28222, Spain
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Santander, 39008, Spain
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Gothenburg, 41345, Sweden
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Linköping, 58185, Sweden
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Lund, SE-22185, Sweden
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Örebro, 701 85, Sweden
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Bournemouth, BH7 7DW, United Kingdom
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Cambridge, CB2 0QQ, United Kingdom
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Leeds, LS9 7TF, United Kingdom
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Leicester, LE1 7RH, United Kingdom
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London, SE5 9RS, United Kingdom
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Plymouth, PL6 8DH, United Kingdom
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Southampton, SO16 6YD, United Kingdom
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Truro, TR1 3LJ, United Kingdom
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Wolverhampton, WV10 0QP, United Kingdom
Related Publications (3)
Sharman JP, Egyed M, Jurczak W, Skarbnik A, Patel K, Flinn IW, Kamdar M, Munir T, Walewska R, Hughes M, Fogliatto LM, Herishanu Y, Banerji V, Follows G, Walker P, Ghia P, Janssens A, Byrd JC, Ferrant E, Ferrajoli A, Wierda WG, Wachira CW, Suterwala BT, Miranda P, Munugalavadla V, Wun CC, Woyach JA. Acalabrutinib-obinutuzumab improves survival vs chemoimmunotherapy in treatment-naive CLL in the 6-year follow-up of ELEVATE-TN. Blood. 2025 Sep 11;146(11):1276-1285. doi: 10.1182/blood.2024024476.
PMID: 40198878DERIVEDKittai AS, Allan JN, James D, Bridge H, Miranda M, Yong ASM, Fam F, Roos J, Shetty V, Skarbnik A, Davids MS. An indirect comparison of acalabrutinib with and without obinutuzumab vs zanubrutinib in treatment-naive CLL. Blood Adv. 2024 Jun 11;8(11):2861-2869. doi: 10.1182/bloodadvances.2023012142.
PMID: 38598745DERIVEDSharman JP, Egyed M, Jurczak W, Skarbnik A, Pagel JM, Flinn IW, Kamdar M, Munir T, Walewska R, Corbett G, Fogliatto LM, Herishanu Y, Banerji V, Coutre S, Follows G, Walker P, Karlsson K, Ghia P, Janssens A, Cymbalista F, Woyach JA, Salles G, Wierda WG, Izumi R, Munugalavadla V, Patel P, Wang MH, Wong S, Byrd JC. Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial. Lancet. 2020 Apr 18;395(10232):1278-1291. doi: 10.1016/S0140-6736(20)30262-2.
PMID: 32305093DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Acerta Clinical Trials
Study Officials
- STUDY DIRECTOR
AstraZeneca Clinical Study Information Center
1-877-240-9479 information.center@astrazeneca.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
June 12, 2015
First Posted
June 19, 2015
Study Start
June 26, 2015
Primary Completion
February 8, 2019
Study Completion
September 30, 2025
Last Updated
August 27, 2025
Results First Posted
January 10, 2023
Record last verified: 2025-08
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.