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Ibrutinib in Treating Patients With Relapsed Hairy Cell Leukemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by National Cancer Institute (NCI)
Information provided by (Responsible Party):
National Cancer Institute (NCI) Identifier:
First received: April 24, 2013
Last updated: February 18, 2015
Last verified: October 2014

This phase II trial studies how well ibrutinib works in treating patients with relapsed hairy cell leukemia. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Condition Intervention Phase
Progressive Hairy Cell Leukemia Initial Treatment
Refractory Hairy Cell Leukemia
Untreated Hairy Cell Leukemia
Drug: Ibrutinib
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter Phase 2 Study of the Bruton's Tyrosine Kinase Inhibitor PCI-32765 (Ibrutinib) for Treatment of Relapsed Hairy Cell Leukemia

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall response rate (CR and PR) [ Time Frame: 32 weeks ] [ Designated as safety issue: No ]
    Calculated as the proportion of patients who achieve a PR or CR to therapy within the first 32 weeks of therapy divided by the total number of evaluable patients.

Secondary Outcome Measures:
  • Incidence of adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 [ Time Frame: Up to 30 days after treatment ] [ Designated as safety issue: Yes ]
    Frequency and severity of adverse events and tolerability of the regimen in each of the patient groups will be collected and summarized by descriptive statistics.

  • Progression-free survival [ Time Frame: From the date of study registration to the date of event or the date of last follow-up if no event has occurred, assessed up to 2 years ] [ Designated as safety issue: No ]
    Kaplan-Meier curves will be used to estimate overall survival and time to next treatment.

  • Overall survival [ Time Frame: From the date of study registration to the date of event or the date of last follow-up if no event has occurred, assessed up to 2 years ] [ Designated as safety issue: No ]
    Kaplan-Meier curves will be used to estimate overall survival and time to next treatment.

  • Rate of molecular remission (MRD-negative CR) defined as resolution of all detectable disease below the limits of detection by immunohistochemistry and 4-color flow cytometry assay [ Time Frame: Up to 32 weeks ] [ Designated as safety issue: No ]
  • Immunologic outcomes during single agent ibrutinib administration [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
  • Expression BRAFV600E in HCL cells [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Protein kinase regulation [ Time Frame: Up to day 29 (day 1 of course 2) ] [ Designated as safety issue: No ]
    Pharmacodynamic effects of BTK inhibition on phospo ERK regulation, as well as other possible protein kinase targets of ibrutinib including B lymphoid tyrosine kinase (Blk) and BMX non-receptor tyrosine kinase (Bmx)/Etk will be assessed.

  • Serum soluble IL-2 receptor level [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • MRD level following maximal response [ Time Frame: Up to 30 days after completing study treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 44
Study Start Date: April 2013
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (ibrutinib)
Patients receive ibrutinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Ibrutinib
Given PO
Other Names:
  • BTK Inhibitor PCI-32765
  • CRA-032765
  • Imbruvica
  • PCI-32765
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Correlative studies
Other Name: pharmacological studies

Detailed Description:


I. To determine the overall response rate (complete response [CR] and partial response [PR]) of hairy cell leukemia (HCL) at 32 weeks after beginning therapy with single-agent ibrutinib.


I. To characterize the toxicity and tolerability of single-agent ibrutinib when administered to patients with HCL.

II. To characterize the progression-free (PFS) and overall survival (OS) of single- agent ibrutinib when administered to patients with HCL.

III. To determine the rate of molecular remission (minimal residual disease [MRD]-negative CR) among all patients, defined as resolution of all detectable disease below the limits of detection by immunohistochemistry and/or 4-color flow cytometry assay at 32 weeks after beginning ibrutinib therapy.

IV. To characterize immunologic outcomes during single agent ibrutinib administration.

V. To explore the effect of PCI-32765 (ibrutinib) on traditional and new biomarkers in HCL including: confirmation of expression v-raf murine sarcoma viral oncogene homolog B V600E mutation (BRAFV600E) in leukemia cells; pharmacodynamic effects of Bruton agammaglobulinemia tyrosine kinase (BTK) inhibition on phospho extracellular signal-regulated kinase (ERK) regulation, as well as other potential protein kinase targets of ibrutinib (exploratory); serum soluble interleukin (IL)-2 receptor correlation with response to ibrutinib therapy; documentation of and quantification of minimal residual disease following maximal response, with flow cytometric analysis and immunohistochemical stains of the bone marrow, as predictors of remission duration after ibrutinib therapy.


Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically confirmed diagnosis of hairy cell leukemia or variant according to World Health Organization (WHO) criteria
  • Hemoglobin < 11 g/dL
  • Platelet count < 100,000/mL
  • Absolute neutrophil count < 1,000/mL
  • Progressive or symptomatic splenomegaly or hepatomegaly
  • Enlarging lymphadenopathy >= 2 cm
  • Absolute lymphocyte count > 5,000/mL
  • Disease related constitutional symptoms consisting of unexplained weight loss exceeding 10% of body weight over the preceding 6 months, Cancer Therapy Evaluation Program (CTEP) active version of the Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or 3 fatigue, fevers > 100.5º Fahrenheit (F) or night sweats for greater than 2 weeks without evidence of infection
  • Patients with classic hairy cell leukemia may receive therapy under the following conditions:

    • After at least 1 prior purine nucleoside analog-containing regimen (fludarabine, pentostatin, or cladribine), or
    • Relapsed or de novo disease if deemed medically unfit for therapy with a purine nucleoside analog

      • Both previously treated and previously untreated patients with this diagnosis will be eligible
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Life expectancy of greater than 12 months
  • Creatinine =< 2.0 mg/dL, and/or creatinine clearance (estimated glomerular filtration rate [GFR] [Cockcroft-Gault]) >= 30 mL/min
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) (unless disease related or due to Gilbert's disease)
  • Aspartate aminotransferase (AST) =< 2 x ULN (unless disease related)
  • Patients will be eligible without respect to baseline peripheral blood cell counts if they otherwise meet inclusion criteria
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 4 months after completion of ibrutinib treatment; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of ibrutinib administration
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients who are receiving any other investigational agents
  • Patients with known brain metastases should be excluded from this clinical trial
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition as ibrutinib
  • Any medications or substances that are strong inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)/5 and/or cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6) (e.g., itraconazole, ketoconazole, clarithromycin, and bupropion) should be discontinued; patients unable to change these medications must be excluded from participation
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with ibrutinib
  • Human immunodeficiency virus (HIV)-positive patients will be eligible unless they have been previously diagnosed with an acquired immune deficiency syndrome (AIDS)-defining illness
  • Patients who require anticoagulation with warfarin (Coumadin) or who have taken warfarin within 28 days prior to enrollment are not eligible; patients who are currently taking vitamin K antagonists are also ineligible for this study
  • Concurrent corticosteroid treatment (equivalent to prednisone > 20 mg daily) is prohibited from 7 days prior to first dose and during treatment with ibrutinib
  • Prior exposure to ibrutinib
  • Major surgery within 10 days or minor surgery within 5 days prior to the first dose of study drug
  • A history of prior malignancy, with the exception of the following:

    • Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years prior to screening, and felt to be at low risk for recurrence by the treating physician
    • Adequately treated non-melanomatous skin cancer or lentigo maligna melanoma without current evidence of disease
    • Adequately treated cervical carcinoma in situ without current evidence of disease
  • Currently active clinically significant cardiovascular disease such as: uncontrolled arrhythmia, congestive heart failure, any class 3 or 4 cardiac disease as defined by the New York Heart Association functional classification or history of myocardial infarction within 6 months prior to first dose with study drug
  • Patient is unable to swallow capsules or has disease significantly affecting gastrointestinal function and/or inhibiting small intestine absorption, such as malabsorption syndrome, resection of the small bowel, or poorly controlled inflammatory bowel disease affecting the small intestine
  • History of stroke or intracranial hemorrhage within 6 months prior to enrollment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01841723

United States, Maryland
Mark O Hatfield-Warren Grant Magnuson Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: Robert J. Kreitman   
Principal Investigator: Robert J. Kreitman         
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Daniel J. DeAngelo    617-632-2645   
Principal Investigator: Daniel J. DeAngelo         
United States, Michigan
Barbara Ann Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Charles A. Schiffer    313-576-8720   
Principal Investigator: Charles A. Schiffer         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Timothy G. Call    507-538-0591   
Principal Investigator: Timothy G. Call         
United States, Ohio
Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Jeffrey A. Jones    614-293-9165   
Principal Investigator: Jeffrey A. Jones         
United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Farhad Ravandi-Kashani    713-745-0394   
Principal Investigator: Farhad Ravandi-Kashani         
Sponsors and Collaborators
Principal Investigator: Jeffrey Jones Ohio State University Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI) Identifier: NCT01841723     History of Changes
Obsolete Identifiers: NCT01981512
Other Study ID Numbers: NCI-2013-00826, NCI-2013-00826, 9268, OSU-12200, 9268, P30CA016058, U01CA076576
Study First Received: April 24, 2013
Last Updated: February 18, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia, Hairy Cell
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms by Histologic Type processed this record on February 27, 2015