Rituximab, Cyclophosphamide, Bortezomib, and Dexamethasone in Treating Patients With Relapsed or Refractory Low-Grade Follicular Lymphoma, Waldenstrom Macroglobulinemia, or Mantle Cell Lymphoma
Condition: Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Nodal Marginal Zone Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia
MeSH terms: Lymphoma; Lymphoma, Follicular; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell; Lymphoma, B-Cell, Marginal Zone; Waldenstrom Macroglobulinemia; Recurrence
Intervention: Bortezomib; Rituximab; Cyclophosphamide; Dexamethasone; Questionnaire Administration; Quality-of-Life Assessment
Intervention description: Given IV; Given IV; Given PO; Given PO; Complete a quality of life questionnaire (FACT/GOG neurotoxicity questionnaire, version 4.0); Complete a quality of life questionnaire (FACT/GOG neurotoxicity questionnaire, version 4.0)
Intervention MeSH terms: Dexamethasone; Cyclophosphamide; Rituximab; Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well giving rituximab and cyclophosphamide together with
      bortezomib and dexamethasone (R-CyBor-D) works in treating patients with relapsed or
      refractory low-grade follicular lymphoma, Waldenstrom macroglobulinemia, or mantle cell
      lymphoma. Monoclonal antibodies, such as rituximab, can block cancer growth in different
      ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and
      help kill them or carry cancer-killing substances to them. Bortezomib may stop the growth of
      cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in
      chemotherapy, such as cyclophosphamide and dexamethasone, work in different ways to stop the
      growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving
      rituximab and bortezomib together with combination chemotherapy may kill more cancer cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histological confirmation of relapsed or refractory follicular Grades 1 or 2 lymphoma,
             mantle cell lymphoma (MCL), small lymphocytic lymphoma/chronic lymphocytic leukemia
             (SLL/CLL), extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid
             tissue (MALT) type, nodal marginal zone B-cell lymphoma, splenic marginal zone B-cell
             lymphoma, or lymphoplasmacytic lymphoma (Waldenstrom's macroglobulinemia/WM) by biopsy
             ≤ 6 months prior to registration

               -  NOTE: MCL diagnosis should be confirmed by cyclin D1 staining or fluorescence in
                  situ hybridization (FISH) (t(11;14))

          -  Measurable disease by computed tomography (CT), positron emission tomography (PET)/CT
             or magnetic resonance imaging (MRI) scans with lymph nodes ≥2.0 cm in at least one
             dimension or tumor cells in the blood ≥ 5 x10^9/L

               -  NOTE: Lymphoplasmacytic lymphoma (WM) patients without lymphadenopathy must have
                  1.) >10% lymphocytes, lymphoplasmacytic cells or plasma cells on a bone marrow
                  aspirate/biopsy, and 2.) quantitative IgM ≥ 400mg/dL

          -  Expected survival > 3 months

          -  ECOG Performance Status (PS) 0, 1 or 2

          -  Absolute Neutrophil Count ≥ 1200

          -  Platelet ≥ 75000

          -  Hemoglobin ≥ 8.0 g/dL

          -  Total bilirubin ≤ 1.5 x upper limit of normal (ULN)

          -  Alkaline phosphatase ≤ 3 x ULN

          -  Aspartate aminotransferase (AST) ≤ 3 x ULN

          -  Creatinine ≤ 1.5 x ULN

          -  Female subject is either postmenopausal for at least 1 year before the screening
             visit, is surgically sterilized or if they are of childbearing potential, agree to
             practice 2 effective methods of contraception from the time of signing the informed
             consent form through 30 days after the last dose of VELCADE (bortezomib), or agree to
             completely abstain from heterosexual intercourse

          -  Male subjects, even if surgically sterilized (i.e., status postvasectomy) must agree
             to 1 of the following: practice effective barrier contraception during the entire
             study treatment period and through a minimum of 30 days after the last dose of study
             drug, or completely abstain from heterosexual intercourse

          -  Voluntary written informed consent before performance of any study-related procedure
             not part of normal medical care, with the understanding that consent may be withdrawn
             by the subject at any time without prejudice to future medical care

          -  Willingness to return to Mayo Clinic institution for follow-up

          -  Negative serum pregnancy test done <7 days prior to registration, for women of
             childbearing potential only

          -  Willingness to complete questionnaires by themselves or with assistance

        Exclusion Criteria:

          -  Any of the following because this study involves an investigational agent whose
             genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are
             unknown:

               -  Pregnant women -- confirmation that the subject is not pregnant must be
                  established by a negative serum B-human chorionic gonadotropin (B-hCG) pregnancy
                  test result obtained during screening. Pregnancy testing is not required for
                  post-menopausal or surgically sterilized women;

               -  Nursing women;

               -  Men or women of childbearing potential who are unwilling to employ adequate
                  contraception

          -  Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
             of the investigator, would make the patient inappropriate for entry into this study or
             interfere significantly with the proper assessment of safety and adverse event of the
             prescribed regimen

          -  Patients known to be human immunodeficiency virus (HIV) positive

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Receiving any other investigational agent which would be considered as a treatment for
             the primary neoplasm

          -  Diagnosed or treated for another malignancy ≤ 3 years prior to registration, with the
             exception of complete resection of basal cell carcinoma or squamous cell carcinoma of
             the skin, an in situ malignancy or low-risk prostate cancer after curative therapy

               -  NOTE: If there is a history of prior malignancy, they must not be receiving other
                  specific treatment (other than hormonal therapy) for their cancer

          -  Patient has received other investigational drugs ≤ 14 days prior to registration

          -  Patient has hypersensitivity to bortezomib, boron or mannitol

          -  Myocardial infarction ≤ 6 months prior to registration or has New York Heart
             Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe
             uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
             ischemia or active conduction system abnormalities

               -  NOTE: Prior to study entry, any electrocardiogram (ECG) abnormality at Screening
                  has to be documented by the investigator as not medically relevant

          -  Previous cancer therapy, hormonal therapy and surgery < 4 weeks prior to registration

          -  Patient has ≥ Grade 2 peripheral neuropathy

          -  Radiation therapy within 3 weeks before randomization

               -  Enrollment of subjects who require concurrent radiotherapy (which must be
                  localized in its field size) should be deferred until the radiotherapy is
                  completed and 3 weeks have elapsed since the last date of therapy