| Eligibility |
Inclusion Criteria:
- Patients must have histologically confirmed indolent B-cell NHL or mantle cell
lymphoma; acceptable subtypes of indolent B-cell NHL include follicular lymphoma
(grades 1, 2, or 3a), marginal zone lymphoma, or lymphoplasmacytic
lymphoma/Waldenstrom's macroglobulinemia; patients with mantle cell lymphoma must have
a documented t(11;14) or overexpression of cyclin D1 by immunohistochemical
evaluation; patients with active large cell transformation are not eligible; however,
patients with a history of large cell transformation are eligible provided that there
is no current clinical evidence of active transformed lymphoma
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- At least one prior therapy; prior autologous or allogeneic stem cell transplant is
allowed; patients may not be on chronic immunosuppressive therapy for
graft-versus-host disease (GVHD); patients who have received prior treatment with a
pan-selective PI3K inhibitor are not eligible; however, prior therapy with a selective
PI3K inhibitor, Bruton's tyrosine kinase inhibitor, or other B-cell receptor targeting
agents is allowed
- Serum creatinine =< 2.0 mg/dL
- Total bilirubin =< upper limit of normal
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.0 x upper limit
of normal
- Absolute neutrophil count (ANC) >= 750/mm^3
- Platelets >= 50,000/ mm^3
- Serum lipase =< upper limit of normal
- Serum amylase =< upper limit of normal
- International normalized ratio (INR) =< 2.0
- Fasting glucose < 120mg/dL
- Recovery to =< grade 1 toxicities associated with prior therapy
- Negative serum pregnancy test; if, on cycle 1 day 1, greater than 72 hours has elapsed
since the last negative result, a serum pregnancy test must be repeated and be
negative on cycle 1 day 1 (C1D1) for the patient to remain eligible
- Patient has the ability and willingness to provide informed consent and has signed the
informed consent document
Exclusion Criteria:
- Pregnant or breast-feeding women and women of childbearing age or men who are
unwilling to use adequate contraception; females of childbearing age and potential
(i.e., not surgically sterilized) must use a second form of contraception, including
total abstinence, intra-uterine device, double-barrier contraception, or other
non-hormonal form of contraception
- Patients with a history of central nervous system involvement by lymphoma
- The presence of co-existing medical conditions that would limit compliance with study
medications, including, but not limited to active infection, active or untreated
cardiac or pulmonary disease, or malignancy
- Patients with significant, symptomatic deterioration of lung function confirmed by
spirometry, diffusion capacity of carbon monoxide (DLCO), or resting oxygen (O2)
saturation
- Patients with impairment of gastrointestinal function that may alter the absorption of
BKM120
- Patients currently being actively treated or who have been treated within the past 3
years for an unrelated malignancy (except non-melanoma skin cancer, cervical carcinoma
in-situ, and low risk prostate cancer)
- Patients who have undergone major surgery within 2 weeks prior to study enrollment or
who have not recovered from a major surgery
- Patients with known human immunodeficiency virus (HIV), hepatitis B or hepatitis C
(active or carriers)
- Patients with a fasting blood glucose >= 120 mg/dL (6.7mmol/L); patients with diabetes
mellitus are eligible if they require oral agents only and have a fasting blood
glucose =< 120 mg/dL; patients with a history of diabetes mellitus who require daily
long-acting or mealtime insulin are not eligible; patients who have previously
required treatment for hyperglycemia due to steroids or other medications are eligible
as long as they have not required insulin or any other oral agent within 2 months
prior to study enrollment
- Patients who are on chronic steroids for unrelated conditions (i.e. rheumatologic
conditions) are not eligible if their total daily dose of steroids is >= 10mg
prednisone
- Patients with a known hypersensitivity to BKM120 or its excipients
- Patients with active moderate or severe major mood or psychiatric disorder as judged
by the investigator, primary care physician, counselor, psychiatrist, or as a result
of the patient's mood assessment questionnaire that may interfere with the ability to
comply with the trial; in addition, given the prior mood-associated toxicities,
patients with a history of psychiatric hospitalization within the past 5 years,
electroconvulsive therapy (ECT) within the past 5 years, or whose psychiatric
condition has been unstable within 2 months prior to study enrollment requiring
addition or change of psychotropic medications are not eligible; examples include, but
are not limited to:
- Medically documented history of or active major depressive episode requiring
inpatient or intensive outpatient therapy, bipolar disorder (I or II),
obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or
active ideation, or homicidal ideation (immediate risk of doing harm to others);
patients under the care of a primary care physician who are treated with one oral
agent and who have not required dose adjustments or new medications within 2
months prior to study enrollment and who otherwise meet eligibility requirements
may be enrolled
- >= Common Terminology for Adverse Events (CTCAE) version 4.0 grade 3 anxiety
- Patients meeting the cutoff score of >= 12 in the Patient Health Questionnaire-9
(PHQ-9) or a cut-off of >= 15 in the Generalized Anxiety Disorder-7 (GAD-7) mood
scale, respectively, or who select a positive response of "1, 2, or 3" to
question number 9 regarding potential for suicidal thoughts in the PHQ-9
(independent of the total score of the PHQ-9) are not eligible
- Patients with diarrhea >= CTCAE grade 2
- Patients with active cardiac disease including any of the following:
- Left ventricular ejection fraction < 50% as determined by multi gated acquisition
scan (MUGA) scan or echocardiogram
- Corrected QT interval (QTc) > 480 msec on screening ECG (using the QTcF formula)
- Active angina pectoris
- Ventricular arrhythmias except for benign premature ventricular contractions
- Supraventricular or nodal arrhythmias or any conduction abnormality requiring a
pacemaker or automatic implantable cardioverter defibrillator (AICD)
- Valvular disease with documented compromise in cardiac function
- Symptomatic pericarditis
- Myocardial infarction within the past 6 months
- Congestive heart failure (New York Heart Association [NYHA] functional
classification III-IV)
- Patients who are currently receiving treatment with medications with a known risk to
prolong the QT interval or inducing Torsades de Pointes and the treatment cannot
either be discontinued or switched to a different medication prior to study enrollment
- Patients who have taken herbal medications and certain fruits within 7 days prior to
study enrollment are not eligible; herbal medications include, but are not limited to,
St John's wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone
(DHEA), yohimbe, saw palmetto, and ginseng; exclusionary fruits include the cytochrome
P450 family 3, subfamily A, polypeptide 4 (CYP3A) inhibitors Seville oranges,
grapefruit, pummelos, or exotic citrus fruits
- Patients who are currently treated with drugs known to be moderate and strong
inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued or
switched to a different medication prior to study enrollment; (please note that
co-treatment with weak inhibitors of CYP3A is allowed)
- Patients who have received oral or IV chemotherapy, targeted anticancer therapy or
radiation therapy =< 4 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C)
prior to study enrollment
- Patients who are currently taking therapeutic doses of warfarin sodium or any other
Coumadin-derivative anticoagulant; patients who can be safely changed to enoxaparin or
other non-warfarin derived anti-coagulant and who otherwise meet eligibility
requirements may be enrolled
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