Adapted from the National Cancer Institute's Physician Data Query (PDQ®)
Cancer Clinical Trials (http://www.cancer.gov/clinicaltrials)
A Multicenter Phase 2 Study of the Bruton's Tyrosine Kinase Inhibitor PCI-32765 for Treatment of Relapsed Hairy Cell Leukemia
Ibrutinib in Treating Patients With Relapsed Hairy Cell Leukemia
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.
To view the NCI PDQ information for this trial, click here
To view the clinicaltrials.gov information for this trial, click here
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 BRAFV600E in leukemia cell; pharmacodynamic effects of 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.
- Histologically confirmed diagnosis of hairy cell leukemia or variant according to World Health Organization (WHO) criteria
- 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 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, or
- Relapsed or de novo disease if deemed medically unfit for therapy with a purine nucleoside analog
- Because there is no recognized standard of care for patients with variant hairy cell leukemia, 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)
- Because patients with HCL are typically pancytopenic at presentation for treatment, patients will be eligible without respect to baseline peripheral blood cell counts if they otherwise meet inclusion criteria
- The effects of ibrutinib on the developing human fetus are unknown; for this reason, and because tyrosine kinase inhibitors may be teratogenic, 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
- 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 because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- Ibrutinib is extensively metabolized by cytochrome P450 (CYP)2D6 and CYP3A4/5; therefore, any medications or substances that are strong inhibitors of CYP3A4/5 and/or CYP2D6 (e.g itraconazole, ketoconazole, clarithromycin, and bupropion) should be discontinued; patients unable to change these medications must be excluded from participation; because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/table.aspx; medical reference texts such as the Physicians' Desk Reference may also provide this information; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
- 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 because ibrutinib is a tyrosine kinase inhibitor with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ibrutinib, 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 due to a potential increased risk of hemorrhage
- 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 4 weeks 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
Chronic Lymphocytic Leukemia (CLL)James Cancer Hospital
National Institutes of Health
OSU Cancer Center
OSU Medical Center