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

NCT01500733 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 2 other identifiers: 12003512-H-0035
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

CLL (Chronic Lymphocytic Leukemia); Leukemia; Leukemia, Lymphocytyc; SLL (Small Lymphocytic Lymphoma)

Keywords

Treatment; CLL (Chronic Lymphocytic Leukemia); SLL (Small Lymphocytic Lymphoma); Leukemia; Lymphocytic Leukemia; Chronic Lymphocytic Leukemia; CLL; Small Lymphocytic Leukemia; SLL

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate at 6 Months

  The primary endpoint was response after 6 cycles of therapy. Overall response rate was calculated as complete response plus partial response, based on the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2008 criteria.as follows: Complete response (CR): all group A and group B criteria are met * Group A criteria: resolution of enlarged lymph nodes, normal size spleen and liver, absolute lymphocyte count \< 4,000/uL, normocellular bone marrow with \< 30% lymphocytes without nodules * Group B criteria: improved blood count (platelet count \> 100,000/uL, hemoglobin \> 11.0 g/dL, neutrophils \> 1,500/uL) Partial response (PR): at least 2 of the group A criteria plus one of the group B criteria are met * Group A criteria: \>=50% decrease in target lymph nodes, \>=50% decrease in spleen size, \>=50% decrease in liver size, 50% reduction in marrow infiltrates * Group B criteria: platelet count \> 100,000/uL, hemoglobin \> 11.0 g/dL, neutrophils \> 1,500/uL

  6 months

Study Arms (2)

Elderly greater than 65

EXPERIMENTAL

Drug: PCI 32765

17p Deletioin

EXPERIMENTAL

Drug: PCI 32765

Interventions

PCI 32765 DRUG

420 mg daily

17p Deletioin; Elderly greater than 65

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cohort 1: Treated and untreated patients age 65 or older and need for therapy
• Cohort 2: Treated (maximum accrual n=16) and untreated (n=27, evaluable) patients at least 18 years old with 17p deletion or p53 expression by immunohistochemistry or p53 mutation by sequencing analysis.
• Men and women with histologically confirmed disease as defined by the following:
• B-lymphocytosis greater than 5000 cells/microL (may be less than 5000 cells/microL if lymphadenopathy is present with histologic confirmation of lymph node involvement by SLL)
• Immunophenotypic profile read by an expert pathologist as consistent with CLL. This will include CD5, CD19, and CD20 expression by the CLL cells typically also with CD23 expression, but CD23 negative cases may be included if there is no t11;14 translocation present.
• Active disease as defined by at least one of the following:
• Weight loss greater than or equal to 10% within the previous 6 months
• Extreme fatigue
• Fevers of greater than 100.5 degrees F for greater than or equal to 2 weeks without evidence of infection
• Night sweats for more than one month without evidence of infection
• Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia
• Massive or progressive splenomegaly
• Massive nodes or clusters or progressive lymphadenopathy
• Progressive lymphocytosis with an increase of greater than 50% over a 2 month period, or an anticipated doubling time of less than 6 months
• Compensated autoimmune hemolysis

You may not qualify if:

• Previous radiotherapy, radioimmunotherapy, biological therapy, chemotherapy, or treatment with an investigational product fpr CCL treatement in the last 4 weeks (i.e. intravenous immunoglobulin).
• Transformed CLL
• Autoimmune hemolytic anemia or thrombocytopenia requiring steroid therapy
• Impaired hepatic function: Total bilirubin greater than or equal to 1.5 times upper limit of normal unless dute to Gilbert's disease, AST/ ALT greater than or equal to 2.5 times institutional upper limit of normal unless due to infiltration of the liver.
• Impaired renal funtion: Creatinine greater than or equal to 2.0 mg/dL or GFR less than or equal to 50ml/min
• Life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of PCI-32765 PO, or put the study outcomes at undue risk
• Concomitant immunotherapy, chemotherapy, radiotherapy, corticosteroids (at dosages equivalent to prednisone \> 20 mg/day), or experimental therapy
• Active Hepatitis B infection
• HIV infection
• Female patients: Current pregnancy or unwilling to take oral contraceptives or refrain from pregnancy if of childbearing potential or currently breastfeeding. Male patients who are unwilling to follow the contraception requirements described in this protocol.
• Psychiatric illness/social situations that would limit the patient s ability to tolerate and/or comply with study requirements.
• Unable to understand the investigational nature of the study or give informed consent.
• Individuals \< 18 yrs old
• Known hypersensitivity to any component of PCI-32765
• Any prior therapy with PCI 32765 or any other BTK inhibitors.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (17)

• 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.

  PMID: 10707771 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. Erratum In: Blood. 2008 Dec 15;112(13):5259.

  PMID: 18216293 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.

  PMID: 18687638 BACKGROUND

• 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.

  PMID: 29483101 RESULT

• 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.

  PMID: 41405491 DERIVED

• 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.

  PMID: 37227160 DERIVED

• 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.

  PMID: 36442911 DERIVED

• 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.

  PMID: 34865212 DERIVED

• 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.

  PMID: 33963002 DERIVED

• 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.

  PMID: 28049639 DERIVED

• 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.

  PMID: 27503501 DERIVED

• 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.

  PMID: 26982511 DERIVED

• 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.

  PMID: 26430171 DERIVED

• 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.

  PMID: 26337493 DERIVED

• 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.

  PMID: 25555420 DERIVED

• 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.

  PMID: 24699307 DERIVED

• 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.

  PMID: 24659631 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Leukemia; Leukemia, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid

Interventions

ibrutinib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Ahn, Inhye
• Organization: National Heart Lung and Blood Institute

inhye.ahn@nih.gov

+1 301 827 1203

Study Officials

• Andy Itsara, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2011
• First Posted: December 28, 2011
• Study Start: January 5, 2012
• Primary Completion: June 20, 2014
• Study Completion (Estimated): September 30, 2034
• Last Updated: April 28, 2026
• Results First Posted: July 11, 2018

Record last verified: 2026-04

Locations

US (1)