PCI-32765 for Special Cases of Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Summary

Background: \- Chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL) are types of blood or lymph node cancers that mostly affect the elderly. CLL/SLL both create abnormal white blood cells that hurt the immune system and make it more difficult to fight infections. These cancers are usually diagnosed after age 50; more than half of the people with CLL/SLL are over age 70. Elderly people often do not respond well to standard chemotherapy for CLL/SLL. They may have other health problems that make chemotherapy difficult. In addition, individuals who have a genetic abnormality called 17p deletion also do not respond well to standard treatments for CLL/SLL. Researchers want to test a new cancer treatment drug, PCI-32765, to see if it can treat CLL/SLL in these hard-to-treat groups. Objectives: \- To see if PCI-32765 is a safe and effective treatment for CLL/SLL in older people and people with 17p deletion. Eligibility: * Individuals over 65 years of age who have CLL/SLL. * Individuals at least 18 years of age who have CLL/SLL and 17p deletion. Design: * Participants will be screened with a medical history, physical exam, and imaging studies. Blood and urine samples will be taken. Optional bone marrow and lymph node biopsies may also be taken. * Participants will take PCI-32765 capsules every day for 28 days (one cycle of treatment). Treatment will be monitored with frequent blood tests and clinic visits. * PCI-32765 will be given for six cycles of treatment. Those who benefit from the drug will continue to take it as long as there are no side effects and the disease does not progress. Those who do not benefit will stop treatment and have regular followup exams.

Timeline

Start

2012-01-05

Primary completion

2014-06-20

Completion

2034-09-30

Publications

• Background Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J. Lymphoma classification--from controversy to consensus: the R.E.A.L. and WHO Classification of lymphoid neoplasms. Ann Oncol. 2000;11 Suppl 1:3-10.
• Background Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Dohner H, Hillmen P, Keating MJ, Montserrat E, Rai KR, Kipps TJ; International Workshop on Chronic Lymphocytic Leukemia. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. 2008 Jun 15;111(12):5446-56. doi: 10.1182/blood-2007-06-093906. Epub 2008 Jan 23.
• Background Rawstron AC, Bennett FL, O'Connor SJ, Kwok M, Fenton JA, Plummer M, de Tute R, Owen RG, Richards SJ, Jack AS, Hillmen P. Monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia. N Engl J Med. 2008 Aug 7;359(6):575-83. doi: 10.1056/NEJMoa075290.
• Results Ahn IE, Farooqui MZH, Tian X, Valdez J, Sun C, Soto S, Lotter J, Housel S, Stetler-Stevenson M, Yuan CM, Maric I, Calvo KR, Nierman P, Hughes TE, Saba NS, Marti GE, Pittaluga S, Herman SEM, Niemann CU, Pedersen LB, Geisler CH, Childs R, Aue G, Wiestner A. Depth and durability of response to ibrutinib in CLL: 5-year follow-up of a phase 2 study. Blood. 2018 May 24;131(21):2357-2366. doi: 10.1182/blood-2017-12-820910. Epub 2018 Feb 26.
• Itsara A, Rogness VM, Samples L, Yuan CM, Wang HW, Ahn IE, Farooqui MZH, Tian X, Sun C, Tomasulo E, Soto S, Superata J, Bezkorovaynaya L, Hughes TE, Nierman P, Wiestner A. A decade of ibrutinib for CLL with and without TP53 aberration: final report on an investigator-sponsored phase 2 study. Blood. 2026 Apr 9;147(15):1702-1712. doi: 10.1182/blood.2025029971.
• Alsadhan A, Chen J, Gaglione EM, Underbayev C, Tuma PL, Tian X, Freeman LA, Baskar S, Nierman P, Soto S, Itsara A, Ahn IE, Sun C, Bibikova E, Hartmann TN, Mhibik M, Wiestner A. CD49d Expression Identifies a Biologically Distinct Subtype of Chronic Lymphocytic Leukemia with Inferior Progression-Free Survival on BTK Inhibitor Therapy. Clin Cancer Res. 2023 Sep 15;29(18):3612-3621. doi: 10.1158/1078-0432.CCR-22-3217.
• Cyr MG, Mhibik M, Qi J, Peng H, Chang J, Gaglione EM, Eik D, Herrick J, Venables T, Novick SJ, Courouble VV, Griffin PR, Wiestner A, Rader C. Patient-derived Siglec-6-targeting antibodies engineered for T-cell recruitment have potential therapeutic utility in chronic lymphocytic leukemia. J Immunother Cancer. 2022 Nov;10(11):e004850. doi: 10.1136/jitc-2022-004850.
• Allan JN, Shanafelt T, Wiestner A, Moreno C, O'Brien SM, Li J, Krigsfeld G, Dean JP, Ahn IE. Long-term efficacy of first-line ibrutinib treatment for chronic lymphocytic leukaemia in patients with TP53 aberrations: a pooled analysis from four clinical trials. Br J Haematol. 2022 Feb;196(4):947-953. doi: 10.1111/bjh.17984. Epub 2021 Dec 5.
• Brieghel C, Aarup K, Torp MH, Andersen MA, Yde CW, Tian X, Wiestner A, Ahn IE, Niemann CU. Clinical Outcomes in Patients with Multi-Hit TP53 Chronic Lymphocytic Leukemia Treated with Ibrutinib. Clin Cancer Res. 2021 Aug 15;27(16):4531-4538. doi: 10.1158/1078-0432.CCR-20-4890. Epub 2021 May 7.
• Ahn IE, Underbayev C, Albitar A, Herman SE, Tian X, Maric I, Arthur DC, Wake L, Pittaluga S, Yuan CM, Stetler-Stevenson M, Soto S, Valdez J, Nierman P, Lotter J, Xi L, Raffeld M, Farooqui M, Albitar M, Wiestner A. Clonal evolution leading to ibrutinib resistance in chronic lymphocytic leukemia. Blood. 2017 Mar 16;129(11):1469-1479. doi: 10.1182/blood-2016-06-719294. Epub 2017 Jan 3.
• Ahn IE, Jerussi T, Farooqui M, Tian X, Wiestner A, Gea-Banacloche J. Atypical Pneumocystis jirovecii pneumonia in previously untreated patients with CLL on single-agent ibrutinib. Blood. 2016 Oct 13;128(15):1940-1943. doi: 10.1182/blood-2016-06-722991. Epub 2016 Aug 8.
• Bitar C, Farooqui MZ, Valdez J, Saba NS, Soto S, Bray A, Marti G, Wiestner A, Cowen EW. Hair and Nail Changes During Long-term Therapy With Ibrutinib for Chronic Lymphocytic Leukemia. JAMA Dermatol. 2016 Jun 1;152(6):698-701. doi: 10.1001/jamadermatol.2016.0225.
• Lipsky AH, Farooqui MZ, Tian X, Martyr S, Cullinane AM, Nghiem K, Sun C, Valdez J, Niemann CU, Herman SE, Saba N, Soto S, Marti G, Uzel G, Holland SM, Lozier JN, Wiestner A. Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib. Haematologica. 2015 Dec;100(12):1571-8. doi: 10.3324/haematol.2015.126672. Epub 2015 Oct 1.
• Sun C, Tian X, Lee YS, Gunti S, Lipsky A, Herman SE, Salem D, Stetler-Stevenson M, Yuan C, Kardava L, Moir S, Maric I, Valdez J, Soto S, Marti GE, Farooqui MZ, Notkins AL, Wiestner A, Aue G. Partial reconstitution of humoral immunity and fewer infections in patients with chronic lymphocytic leukemia treated with ibrutinib. Blood. 2015 Nov 5;126(19):2213-9. doi: 10.1182/blood-2015-04-639203. Epub 2015 Sep 3.
• Farooqui MZ, Valdez J, Martyr S, Aue G, Saba N, Niemann CU, Herman SE, Tian X, Marti G, Soto S, Hughes TE, Jones J, Lipsky A, Pittaluga S, Stetler-Stevenson M, Yuan C, Lee YS, Pedersen LB, Geisler CH, Calvo KR, Arthur DC, Maric I, Childs R, Young NS, Wiestner A. Ibrutinib for previously untreated and relapsed or refractory chronic lymphocytic leukaemia with TP53 aberrations: a phase 2, single-arm trial. Lancet Oncol. 2015 Feb;16(2):169-76. doi: 10.1016/S1470-2045(14)71182-9. Epub 2014 Dec 31.
• Herman SE, Niemann CU, Farooqui M, Jones J, Mustafa RZ, Lipsky A, Saba N, Martyr S, Soto S, Valdez J, Gyamfi JA, Maric I, Calvo KR, Pedersen LB, Geisler CH, Liu D, Marti GE, Aue G, Wiestner A. Ibrutinib-induced lymphocytosis in patients with chronic lymphocytic leukemia: correlative analyses from a phase II study. Leukemia. 2014 Nov;28(11):2188-96. doi: 10.1038/leu.2014.122. Epub 2014 Apr 4.
• Herman SE, Mustafa RZ, Gyamfi JA, Pittaluga S, Chang S, Chang B, Farooqui M, Wiestner A. Ibrutinib inhibits BCR and NF-kappaB signaling and reduces tumor proliferation in tissue-resident cells of patients with CLL. Blood. 2014 May 22;123(21):3286-95. doi: 10.1182/blood-2014-02-548610. Epub 2014 Mar 21.

Drugs

Indications