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

NCT02049541 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-13027NCI-2014-00110
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

Keywords

BKM120; B-Cell Lymphoma; PI3K inhibitor

Outcome Measures

Primary Outcomes (1)

• MTD defined as the dose level at which no more than one of 6 patients experiences a DLT summarized using the National Cancer Institute (NCI) CTCAE version 4.0

  Summarized and tabulated by dose level.

  28 days

Secondary Outcomes (3)

• Incidence of grade 3 or greater adverse events summarized using the NCI CTCAE version 4.0

  Up to 5 years

• Overall response rate (ORR) evaluated by computed tomography (CT) or positron emission tomography (PET)/CT

  Up to 5 years

• Change in correlative markers in blood, bone marrow and tumor tissue

  Baseline to up to 5 years

Study Arms (1)

Treatment (PI3K inhibitor BKM120, rituximab)

EXPERIMENTAL

Patients receive BKM120 PO daily and rituximab IV. 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. Pharmacodynamic samples from peripheral blood (for those with peripheral blood involvement) and bone marrow aspirate (for all patients) are drawn at baseline. Patients will undergo correlative studies to include bone marrow biopsy at study enrollment, and at the time of complete remission.

Drug: PI3K inhibitor BKM120; Biological: rituximab; Other: Pharmacodynamics; Other: Correlative studies

Interventions

PI3K inhibitor BKM120 DRUG

Will be supplied to each patient on the first day of each cycle. It will subsequently be self administered by the patient themselves daily on days 1-28 of every 28 day cycle

Also known as: BKM120, PI3K_Inhibitor_BKM120

Treatment (PI3K inhibitor BKM120, rituximab)

rituximab BIOLOGICAL

Given IV (intervenously) on days 2, 8, 15, and 22 of cycle 1, and subsequently on day 1 of cycles 3, 5, 7, 9, and 11.

Also known as: IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan

Treatment (PI3K inhibitor BKM120, rituximab)

Pharmacodynamics OTHER

Pharmacodynamic samples from peripheral blood (for those with peripheral blood involvement) and bone marrow aspirate (for all patients) are drawn at baseline.

Also known as: pharmacological studies, Correlative studies

Treatment (PI3K inhibitor BKM120, rituximab)

Correlative studies OTHER

Patients will undergo correlative studies to include bone marrow biopsy at study enrollment, and at the time of complete remission. In addition, patients with peripheral blood involvement at enrollment will have peripheral blood drawn for all planned research correlates.

Also known as: laboratory biomarker analysis

Treatment (PI3K inhibitor BKM120, rituximab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Kami Maddocks, MD: lead
• Novartis: collaborator

Study Sites (2)

Emory University

Atlanta, Georgia, 30322, United States

Location

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Lymphoma, B-Cell, Marginal Zone; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Waldenstrom Macroglobulinemia; Lymphoma, B-Cell

Interventions

NVP-BKM120; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Kami Maddocks, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 28, 2014
• First Posted: January 30, 2014
• Study Start: July 21, 2014
• Primary Completion: September 12, 2018
• Study Completion: April 9, 2019
• Last Updated: June 30, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)