LeukemiaPhase 2NCT01500733
PCI-32765 for Special Cases of Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
A Phase 2 study testing PCI 32765 in people with Leukemia and Leukemia, Lymphocytyc, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Leukemia, Lymphocytyc, CLL (Chronic Lymphocytic Leukemia)
- What is being tested?
- PCI 32765
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 86 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Jan 2012to 30 Sep 2034
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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
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- 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.
- Requires anticoagulation with warfarin.
- Requires treatment with strong CY3A4/5 and/or CYP2D6 inhibitors (unless no alternative is available).
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: A Phase II Study of PCI-32765 for Patients With Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) Who Need Therapy and Are Older Than 65 or Have a 17p Deletion
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.
Read more
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.
Read the detailed description
CLL/SLL is a malignancy of B cells that predominantly affects the elderly population. Diagnosis is typically made in adults over the age of 50 and more than half of the people with CLL/SLL are over the age of 70. Elderly patients in particular have other comorbidities that limit the tolerability of standard CLL/SLL chemoimmunotherapy regimens and they often have inferior response to these particular regimens. In addition, those patients with a 17p deletion also have inferior outcomes due to rapid progression of disease as well as refractoriness to standard treatment regimens.
It is still unclear what leads to the development of CLL/SLL. However, recent studies indicated that B cell receptor (BCR) signaling is an important contributor to the disease and could be a target for therapy. Bruton s Tyrosine Kinase (Btk) is an enzyme required for BCR signaling.
Ibrutinib is a potent and selective inhibitor of Bruton Tyrosine Kinase (Btk). In vitro lymphoma models have demonstrated that ibrutinib inhibits Btk. Inhibition of Btk blocks downstream BCR signaling pathways and thus prevents B cell proliferation. A phase 1 study of ibrutinib shows activity in multiple lymphomas including CLL/SLL.
This study will investigate the efficacy of ibrutinib for patients with CLL/SLL in patients that are older than 65 who are in need of therapy.This protocol is intended both for patients who have been untreated and those who have undergone other therapies.
- Conditions
- Leukemia, Leukemia, Lymphocytyc, CLL (Chronic Lymphocytic Leukemia), SLL (Small Lymphocytic Lymphoma)
- Being tested
- PCI 32765
- Keywords
- Treatment, CLL (Chronic Lymphocytic Leukemia), SLL (Small Lymphocytic Lymphoma), Leukemia, Lymphocytic Leukemia, Chronic Lymphocytic Leukemia, CLL, Small Lymphocytic Leukemia, SLL
- Medical subject headings
- Leukemia, Leukemia, B-Cell, Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Lymphoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PCI 32765Drug
420 mg daily
| Study group | Role | What they receive |
|---|---|---|
| Elderly greater than 65 | Experimental | Not described Receives: Drug: PCI 32765 |
| 17p Deletioin | Experimental | Not described Receives: Drug: PCI 32765 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2011 (estimated)
- Study start5 Jan 2012
- Primary completion20 Jun 2014
- Study completion30 Sep 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (17)Papers the sponsor has linked to this study.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 86 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Andy Itsara, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01500733
- Sponsor's protocol ID
- 120035
- Other IDs
- 12-H-0035
- Status last verified
- Apr 2026
- First submitted
- 22 Dec 2011
- Last updated
- 28 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 10707771Hallek 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.
PubMed 18216293Rawstron 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.
PubMed 18687638Ahn 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.
PubMed 29483101Itsara 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.
PubMed 41405491Alsadhan 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.
PubMed 37227160Cyr 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.
PubMed 36442911Allan 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.
PubMed 34865212Brieghel 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.
PubMed 33963002Ahn 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.
PubMed 28049639Ahn 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.
PubMed 27503501Bitar 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.
PubMed 26982511Lipsky 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.
PubMed 26430171Sun 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.
PubMed 26337493Farooqui 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.
PubMed 25555420