New hope for CLL: acalabrutinib takes on standard therapy in major trial

NCT ID NCT02970318

Disease control Sponsor: Acerta Pharma BV Source: ClinicalTrials.gov ↗

First seen Jun 26, 2026 · Last updated Jul 24, 2026 · Updated 2 times

Summary

This phase 3 trial compares the targeted drug acalabrutinib against two standard combination therapies (idelalisib plus rituximab or bendamustine plus rituximab) in 310 adults with chronic lymphocytic leukemia (CLL) that has returned or not responded to prior treatment. The main goal is to see if acalabrutinib alone can delay cancer progression better than the other options. The study is active but no longer recruiting, and final results are being analyzed.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: Acalabrutinib
What this could lead to: If successful, acalabrutinib could offer a more effective and possibly better-tolerated option for people with CLL that has returned or not responded to prior treatment.
What could go wrong: This is a late-stage trial, but results may not apply to all CLL patients. Acalabrutinib may still have side effects, and it is not a cure—patients will need ongoing monitoring.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 3

Large-scale testing in a bigger group. Usually the last step before a treatment can be approved.

Participants

310 people

The number who actually took part.

Started

Feb 2017

Expected to finish

Oct 2027

An estimate. End dates often move.

Lead sponsor

A company

The lead sponsor is a pharmaceutical, biotech, or medical-device company.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: 1. Men and women ≥ 18 years of age. 2. ECOG performance status of 0 to 2. 3. Diagnosis of CLL that meets published diagnostic criteria (Hallek 2008): 1. 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. 2. Prolymphocytes may comprise ≤ 55% of blood lymphocytes. 3. Presence of ≥ 5 x 10\^9 B lymphocytes/L (5000/μL) in the peripheral blood (at any point since initial diagnosis). 4. Must have documented CD20-positive CLL. 5. Active disease meeting ≥ 1 of the following IWCLL 2008 criteria for requiring treatment: 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 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. 5. Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy. 6. 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. ii. Significant fatigue (ECOG performance score 2; inability to work or perform usual activities). iii. Fevers higher than 100.5°F or 38.0°C for ≥ 2 weeks before screening without evidence of infection. iv. Night sweats for \> 1 month before screening without evidence of infection. 6. Meet the following laboratory parameters: 1. ANC ≥ 750 cells/μL (0.75 x 10\^9/L), or ≥ 500 cells/μL (0.50 x 10\^9/L) in subjects with documented bone marrow involvement, and independent of growth factor support 7 days before assessment. 2. Platelet count ≥ 50,000 cells/μL (50 x 10\^9/L), or ≥ 30,000 cells/μL (30 x 10\^9/L) in subjects with documented bone marrow involvement, and without transfusion support 7 days before assessment. Subjects with transfusion-dependent thrombocytopenia are excluded. If an Investigator has chosen bendamustine/rituximab as the Arm B treatment, platelets must be ≥ 75,000 cells/μL (75 x 10\^9/L). 3. Serum AST and ALT ≤ 2.0 x ULN. 4. Total bilirubin ≤ 1.5 x ULN. 5. Estimated creatinine clearance of ≥ 30 mL/min, calculated using the formula of Cockcroft and Gault \[(140-Age) • Mass (kg)/(72 • creatinine mg/dL); multiply by 0.85 if female\]. 7. Must have received ≥ 1 prior systemic therapies for CLL. Note: Single-agent steroids or localized radiation are not considered a prior line of therapy. If a single-agent anti-CD20 antibody was previously administered, subjects must have received ≥ 2 doses. 8. Women who are sexually active and can bear children must agree to use highly effective forms of contraception while on the study and for 2 days after the last dose of acalabrutinib, 90 days after the last dose of idelalisib, 6 months after the last dose of bendamustine, or 12 months after the last dose of rituximab, whichever is longer. Highly effective forms of contraception are defined in Section 9.2.5. 9. Men who are sexually active and can beget children must agree to use highly effective forms of contraception during the study and for 90 days after the last dose of idelalisib, 6 months after the last dose of bendamustine, or 12 months after the last dose of rituximab, whichever is longer. Highly effective forms of contraception are defined in Section 9.2.5. 10. Men must agree to refrain from sperm donation during the study and for 90 days after the last dose of idelalisib, 6 months after the last dose of bendamustine, or 12 months after the last dose of rituximab, whichever is longer. 11. Willing and able to participate in all required evaluations and procedures in this study protocol, including swallowing capsules without difficulty. 12. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local patient privacy regulations). Exclusion Criteria: 1. Known CNS lymphoma or leukemia. 2. Known prolymphocytic leukemia or history of, or currently suspected, Richter's syndrome. 3. 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). 4. 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. 5. Received any chemotherapy, external beam radiation therapy, anticancer antibodies, or investigational drug within 30 days before first dose of study drug. 6. 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. 7. Prior radio- or toxin-conjugated antibody therapy. 8. 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. 9. 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. 10. History of prior malignancy except for the following: 1. 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. 2. Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled nonmelanomatous skin cancer. 3. Adequately treated carcinoma in situ without current evidence of disease. 11. 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. 12. 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. 13. Received a live virus vaccination within 28 days of first dose of study drug. 14. Known history of infection with HIV or any uncontrolled active systemic infection (e.g., bacterial, viral, or fungal). For study sites in Germany: active infection with human immunodeficiency virus (seropositivity for HIV-1 or HIV-2 antibodies, and if positive, reactivity against the HIV-specific p24 antigen). 15. Active CMV infection (active viremia as evidenced by positive polymerase chain reaction \[PCR\] result for CMV DNA). 16. Serologic status reflecting active hepatitis B or C infection. 1. Subjects who are anti-HBc positive and who are surface antigen negative will need to have a negative PCR result before randomization. Those who are HbsAg-positive or hepatitis B PCR positive will be excluded. 2. Subjects who are hepatitis C antibody positive will need to have a negative PCR result before randomization. Those who are hepatitis C PCR positive will be excluded. 17. Ongoing, drug-induced liver injury, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, ongoing extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension. 18. History of or ongoing drug-induced pneumonitis. 19. History of serious allergic reactions including anaphylaxis and toxic epidermal necrolysis. 20. History of stroke or intracranial hemorrhage within 6 months before first dose of study drug. 21. History of bleeding diathesis (e.g., hemophilia, von Willebrand disease). 22. Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon) within 7 days of first dose of study drug. 23. Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening. 24. Requires treatment with a strong CYP3A inhibitor/inducer. 25. Requires treatment with proton-pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Subjects receiving proton-pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrollment to this study. 26. Breast feeding or pregnant. 27. Concurrent participation in another therapeutic clinical trial. 28. Prothrombin time/INR or aPTT (in the absence of a Lupus anticoagulant) \> 2.0 x ULN. Exception: Subjects receiving warfarin are excluded, however, those receiving other anticoagulant therapy who have a higher INR/aPTT may be permitted to enroll to this study after discussion with the medical monitor. 29. History of confirmed progressive multifocal leukoencephalopathy (PML)

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Conditions

The condition(s) this trial relates to.

B-cell chronic lymphocytic leukemia

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Chronic lymphocytic leukemia

Contacts and locations

Locations

Research Site

Chandler, Arizona, 85224, United States
Research Site

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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Southampton, SO16 6YD, United Kingdom
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Wolverhampton, WV10 0QP, United Kingdom
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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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Nový Hradec Králové, 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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München, 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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Kaposvár, 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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Luleå, 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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