Carfilzomib With or Without Rituximab in the Treatment of Waldenstrom Macroglobulinemia or Marginal Zone Lymphoma
Condition: Marginal Zone Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Waldenstrom Macroglobulinemia; Refractory Marginal Zone Lymphoma; Refractory Waldenstrom Macroglobulinemia; Waldenstrom Macroglobulinemia
MeSH terms: Lymphoma; Lymphoma, B-Cell, Marginal Zone; Waldenstrom Macroglobulinemia; Recurrence
Intervention: Carfilzomib; Laboratory Biomarker Analysis; Rituximab
Intervention description: Given IV; Correlative studies; Given IV
Intervention MeSH terms: Rituximab; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well carfilzomib with or without rituximab work in treating
      patients with Waldenstrom macroglobulinemia or marginal zone lymphoma that is previously
      untreated, has come back, or does not respond to treatment. Carfilzomib may stop the growth
      of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with
      monoclonal antibodies, such as rituximab, may induce changes in body's immune system and may
      interfere with the ability of tumor cells to grow and spread. Giving carfilzomib alone when
      disease is responding or with rituximab when disease is not responding may work better in
      treating patients with Waldenstrom macroglobulinemia or marginal zone lymphoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Waldenstrom's macroglobulinemia (WM) or marginal zone lymphoma (MZL) based on
             institutional pathology review; patients may have either previously untreated or
             relapsed/refractory disease

          -  Measurable disease: for WM presence of monoclonal IgM immunoglobulin concentration on
             serum electrophoresis, with lymphoplasmacytic marrow infiltrate; for MZL: measurable
             nodal disease measuring at least 1.5 cm in longest dimension, or splenomegaly

          -  Indication for initiation of therapy

          -  Absolute neutrophil count (ANC) > 1,000/uL unless disease-related (due to marrow
             infiltration or splenomegaly)

          -  Platelet count > 75,000/uL unless disease-related (due to marrow infiltration or
             splenomegaly)

          -  Serum creatinine < 2.5 mg/dL or creatinine clearance > 30 cc/min

          -  Bilirubin < 2 x upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x ULN

          -  All patients must be informed of the investigational nature of this study and have
             given written consent in accordance with institutional and federal guidelines

          -  Expected survival of > 90 days

          -  Females of childbearing potential (FCBP) must agree to pregnancy testing and to
             practice contraception

          -  Male subjects must agree to practice contraception

        Exclusion Criteria:

          -  Known human immunodeficiency virus (HIV), hepatitis C, or hepatitis B positivity
             (subjects with hepatitis B surface antigen [SAg] or core antibody positivity, who are
             receiving and responding to antiviral therapy directed at hepatitis B or are negative
             for hepatitis B virus [HBV] deoxyribonucleic acid [DNA], are allowed)

          -  Candidate for potentially curative antibiotic therapy for gastric mucosa-associated
             lymphoid tissue (MALT); (gastric MALT lymphoma patients with stage I/II helicobacter
             [H.] pylori positive lymphoma must fail therapy with H.-pylori directed therapy before
             being considered for this study)

          -  Eastern Cooperative Oncology Group (ECOG) performance status 3 or higher

          -  Known active central nervous system (CNS) involvement

          -  Pregnant or lactating females

          -  Inadequate cardiac function, as measured by left ventricular ejection fraction (LVEF)
             that is less than or equal to 40%, or the presence of New York Heart Association
             (NYHA) classification of greater than stage II congestive heart failure

          -  Significant neuropathy (grades 3-4, or grade 2 with pain) within 14 days prior to
             screening

          -  Uncontrolled inter-current illness including, but not limited to, unstable angina,
             recent myocardial infarction within 6 months of screening and uncontrolled cardiac
             arrhythmias, psychiatric illness, or psychosocial difficulty that would limit
             compliance with study requirements

          -  Non-hematologic malignancy within the past 3 years with the exception of a) adequately
             treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b)
             carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason grade 6 or
             less with stable prostate-specific antigen levels; or d) cancer considered cured by
             surgical resection or unlikely to impact survival during the duration of the study