Trial Title:
Ibrutinib in Treating Patients With Relapsed Hairy Cell Leukemia
NCT ID:
NCT01841723
Condition:
Hairy Cell Leukemia
Hairy Cell Leukemia Variant
Recurrent Hairy Cell Leukemia
Recurrent Hairy Cell Leukemia Variant
Conditions: Official terms:
Leukemia
Leukemia, Hairy Cell
Recurrence
Ibrutinib
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (ibrutinib)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Bone Marrow Aspiration
Description:
Undergo bone marrow aspiration and biopsy
Arm group label:
Treatment (ibrutinib)
Intervention type:
Procedure
Intervention name:
Bone Marrow Biopsy
Description:
Undergo bone marrow aspiration and biopsy
Arm group label:
Treatment (ibrutinib)
Other name:
Biopsy of Bone Marrow
Other name:
Biopsy, Bone Marrow
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Treatment (ibrutinib)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Drug
Intervention name:
Ibrutinib
Description:
Given PO
Arm group label:
Treatment (ibrutinib)
Other name:
BTK Inhibitor PCI-32765
Other name:
CRA 032765
Other name:
CRA-032765
Other name:
CRA032765
Other name:
Imbruvica
Other name:
PCI 32765
Other name:
PCI-32765
Other name:
PCI32765
Intervention type:
Procedure
Intervention name:
Ultrasound Imaging
Description:
Undergo ultrasound
Arm group label:
Treatment (ibrutinib)
Other name:
2-Dimensional Grayscale Ultrasound Imaging
Other name:
2-Dimensional Ultrasound Imaging
Other name:
2D-US
Other name:
Ultrasonography
Other name:
Ultrasound
Other name:
Ultrasound Test
Other name:
Ultrasound, Medical
Other name:
US
Summary:
This phase II trial studies how well ibrutinib works in treating patients with hairy cell
leukemia that has returned after a period of improvement. Ibrutinib may stop the growth
of cancer cells by blocking some of the enzymes needed for cell growth.
Detailed description:
PRIMARY OBJECTIVE:
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.
SECONDARY OBJECTIVES:
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 ibrutinib (PCI-32765) on traditional and new biomarkers in
HCL including:
Va. Confirmation of expression BRAFV600E in leukemia cells Vb. Pharmacodynamic effects of
BTK inhibition on phosphorylated (phospho) ERK regulation, as well as other potential
protein kinase targets of ibrutinib (exploratory) Vc. Serum soluble IL-2 receptor
correlation with response to ibrutinib therapy Vd. 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.
OUTLINE:
Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every
28 days for up to 8 cycles if lack of response to therapy, up to 12 cycles if failure to
achieve an objective response (CR/PR), or continually at per physician discretion in the
absence of disease progression or unacceptable toxicity. Additionally, patients undergo
bone marrow aspiration and biopsy, blood sample collection, and computed tomography (CT)
or ultrasound throughout the study.
After completion of study treatment, patients are followed up every 3 months.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Histologically confirmed diagnosis of hairy cell leukemia or variant according to
World Health Organization (WHO) criteria with any of the following indications for
therapy:
- 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 > 100.5 degrees 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
- 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
- Age ≥ 18 years. Because no dosing or adverse event data are currently available on
the use of ibrutinib in patients < 18 years of age, children are excluded from this
study, but may be eligible for future pediatric trials
- 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) =< 3.0 x ULN (unless disease related)
- Prothrombin time (PT)/international normalized ratio (INR) < 1.5 x ULN
- Partial thromboplastin time (PTT) (activated partial thromboplastin time [aPTT]) <
1.5 x ULN
- 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; female patients who are
of non-reproductive potential (i.e., post-menopausal by history - no menses for >= 1
year; or history of hysterectomy; or history of bilateral tubal ligation; or history
of bilateral oophorectomy); female patients of childbearing potential must have a
negative serum pregnancy test upon study entry; male and female patients who agree
to use highly effective methods of birth control (e.g., condoms, implants,
injectables, combined oral contraceptives, some intrauterine devices [IUDs],
complete sexual abstinence, or sterilized partner) during the period of therapy and
for 90 days after the last dose of study drug; 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
- Ability to understand and the willingness to sign a written informed consent
document
Exclusion Criteria:
- Chemotherapy =< 21 days prior to first administration of study treatment and/or
monoclonal antibody =< 6 weeks prior to first administration of study treatment
- 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
- History of allergic reactions attributed to compounds of similar chemical or
biologic composition as ibrutinib
- Ibrutinib is extensively metabolized by CYP3A4/5; patients who received a strong
cytochrome P450 (CYP) 3A inhibitor within 7 days prior to the first dose of
ibrutinib or patients who require continuous treatment with a strong CYP3A
inhibitor; therefore, any medications or substances that are strong inhibitors of
CYP3A4/5 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; 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; recent infections requiring systemic treatment need to have
completed therapy > 14 days before the first dose of study drug
- 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; patients who are currently taking vitamin K
antagonists are also ineligible for this study
- Patients requiring daily corticosteroids at a prednisone equivalent of >= 20 mg
daily should not be enrolled; if corticosteroids can be discontinued (or reduced to
< 20 mg per day of prednisone or equivalent), the discontinuation or dose reduction
should be done at least 7 days prior to first dose
- Prior exposure to a Bruton's tyrosine kinase (BTK) inhibitor
- Major surgery within 4 weeks of 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, or class 3 or 4 congestive heart failure as
defined by the New York Heart Association Functional Classification or history of
myocardial infarction, unstable angina, or acute coronary syndrome within 6 months
prior to first dose with study drug
- Patient is unable to swallow capsules, or has disease significantly affecting
gastrointestinal function or resection of the stomach or small bowel, or symptomatic
inflammatory bowel disease or ulcerative colitis, or partial or complete bowel
obstruction
- History of stroke or intracranial hemorrhage within 6 months prior to enrollment
- Serologic status reflecting active hepatitis B or C infection; patients that are
positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or
hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to
enrollment; (PCR positive patients will be excluded)
- Concurrent systemic immunosuppressant therapy other than corticosteroids (e.g.,
cyclosporine A, tacrolimus, etc.) within 28 days of the first dose of study drug
- Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug
- Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved
to Common Terminology Criteria for Adverse Event (CTCAE, version 5), grade =< 1, or
to the levels dictated in the inclusion/exclusion criteria with the exception of
alopecia
- Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia
- Unwilling or unable to participate in all required study evaluations and procedures
- Currently active, clinically significant hepatic impairment (>= moderate hepatic
impairment according to the National Cancer Institute [NCI]/Child Pugh
classification)
- Incarceration at time of enrollment; prisoners will be excluded from enrollment;
subjects who become incarcerated after starting study treatment will be allowed to
continue in the study
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
National Institutes of Health Clinical Center
Address:
City:
Bethesda
Zip:
20892
Country:
United States
Facility:
Name:
Wayne State University/Karmanos Cancer Institute
Address:
City:
Detroit
Zip:
48201
Country:
United States
Facility:
Name:
Mayo Clinic in Rochester
Address:
City:
Rochester
Zip:
55905
Country:
United States
Facility:
Name:
Ohio State University Comprehensive Cancer Center
Address:
City:
Columbus
Zip:
43210
Country:
United States
Facility:
Name:
M D Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Start date:
April 30, 2013
Completion date:
December 31, 2024
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Cancer Institute (NCI)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT01841723
