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About
This phase I clinical trial studies the side effects and the best dose of phosphatidylinositol-3-kinase (PI3K) inhibitor BKM120 when given together with rituximab in treating patients with relapsed or refractory low-grade B-cell lymphoma. PI3K inhibitor BKM120 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving PI3K inhibitor BKM120 with rituximab may be an effective treatment for B-cell lymphoma.
Full description
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of combined rituximab and BKM120 (PI3k inhibitor BKM120) in patients with previously treated indolent non-Hodgkin lymphoma (NHL) (including follicular lymphoma (FL), marginal zone lymphoma, and lymphoplasmacytic lymphoma/Waldenstrom's macroglobulinemia), and mantle cell lymphoma (MCL).
SECONDARY OBJECTIVES:
I. To determine specific toxicities associated with combined BKM120 and rituximab.
II. Evaluate for efficacy of BKM120 in combination with rituximab in these diseases.
OUTLINE: This is a dose-escalation study of PI3K inhibitor BKM120.
Patients receive PI3K inhibitor BKM120 orally (PO) daily on days 1-28 and rituximab intravenously (IV) on days 2, 8, 15, and 22 of course 1 and on day 1 of courses 3, 5, 7, 9, and 11. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with asymptomatic progression may continue treatment for up to 12 months.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
Enrollment
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Inclusion criteria
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:
Patients with diarrhea >= CTCAE grade 2
Patients with active cardiac disease including any of the following:
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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18 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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