Acalabrutinib and Venetoclax Treatment of Newly Diagnosed Patients With CLL at High Risk of Infection or Early Treatment

Summary

Many patients with CLL have a weakened immune system due to their disease. It increases their risk of developing serious, treatment-requiring infections such as blood poisoning or pneumonia, which in the worst case may end with fatal outcomes. Serious infections due to CLL are responsible for one third of all deaths among CLL patients. PreVent-ACaLL study will investigate whether a combination of two known types of cancer drugs can reduce the risk of infection and thus mortality when given preventively to newly diagnosed CLL patients. A newly developed register-based computer model can predict which patients are at high risk in order to develop infections as a result of their CLL. A preventive treatment might be initiated before patients need chemotherapy. In this way, the cancer disease might be "reset" so that the immune system, which is inhibited by CLL, is restored and the risk of fatal infections is minimized.

Timeline

Start

2019-10-11

Primary completion

2029-07-31

Completion

2030-07-31

Publications

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• Background de Rooij MF, Kuil A, Geest CR, Eldering E, Chang BY, Buggy JJ, Pals ST, Spaargaren M. The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia. Blood. 2012 Mar 15;119(11):2590-4. doi: 10.1182/blood-2011-11-390989. Epub 2012 Jan 25.
• Background Khan WN. Regulation of B lymphocyte development and activation by Bruton's tyrosine kinase. Immunol Res. 2001;23(2-3):147-56. doi: 10.1385/IR:23:2-3:147.
• Background Mohamed AJ, Yu L, Backesjo CM, Vargas L, Faryal R, Aints A, Christensson B, Berglof A, Vihinen M, Nore BF, Smith CI. Bruton's tyrosine kinase (Btk): function, regulation, and transformation with special emphasis on the PH domain. Immunol Rev. 2009 Mar;228(1):58-73. doi: 10.1111/j.1600-065X.2008.00741.x.
• Background Ponader S, Chen SS, Buggy JJ, Balakrishnan K, Gandhi V, Wierda WG, Keating MJ, O'Brien S, Chiorazzi N, Burger JA. The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo. Blood. 2012 Feb 2;119(5):1182-9. doi: 10.1182/blood-2011-10-386417. Epub 2011 Dec 16.
• Background Smith TJ, Khatcheressian J, Lyman GH, Ozer H, Armitage JO, Balducci L, Bennett CL, Cantor SB, Crawford J, Cross SJ, Demetri G, Desch CE, Pizzo PA, Schiffer CA, Schwartzberg L, Somerfield MR, Somlo G, Wade JC, Wade JL, Winn RJ, Wozniak AJ, Wolff AC. 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol. 2006 Jul 1;24(19):3187-205. doi: 10.1200/JCO.2006.06.4451. Epub 2006 May 8.
• Background Soucek L, Buggy JJ, Kortlever R, Adimoolam S, Monclus HA, Allende MT, Swigart LB, Evan GI. Modeling pharmacological inhibition of mast cell degranulation as a therapy for insulinoma. Neoplasia. 2011 Nov;13(11):1093-100. doi: 10.1593/neo.11980.
• Narkhede M, Ujjani CS. Immune Dysfunction and Consequences in Chronic Lymphocytic Leukemia. J Natl Compr Canc Netw. 2025 Mar;23(3):e247090. doi: 10.6004/jnccn.2024.7090.
• Svanberg Teglgaard R, Marquart HV, Hartling HJ, Bay JT, da Cunha-Bang C, Brieghel C, Faitova T, Enggaard L, Kater AP, Levin MD, Kersting S, Ostrowski SR, Niemann CU. Improved Innate Immune Function in Patients with Chronic Lymphocytic Leukemia Treated with Targeted Therapy in Clinical Trials. Clin Cancer Res. 2024 May 1;30(9):1959-1971. doi: 10.1158/1078-0432.CCR-23-2522.
• Gargiulo E, Teglgaard RS, Faitova T, Niemann CU. Immune Dysfunction and Infection - Interaction between CLL and Treatment: A Reflection on Current Treatment Paradigms and Unmet Needs. Acta Haematol. 2024;147(1):84-98. doi: 10.1159/000533234. Epub 2023 Jul 27.

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