Study of BKM120 & Rituximab in Patients With Relapsed or Refractory Indolent B-Cell Lymphoma

This is an interventional treatment trial for Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue focused on measuring BKM120, B-Cell Lymphoma, PI3K inhibitor Read More

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