Bortezomib and Rituximab in Treating Patients With Mantle Cell Lymphoma Who Have Previously Undergone Stem Cell Transplantation
Condition: Contiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Stage I Mantle Cell Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Mantle Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, Mantle-Cell
Intervention: bortezomib; rituximab; laboratory biomarker analysis; immunohistochemistry staining method; RNA analysis; gene expression analysis; DNA analysis; pharmacological study; pharmacogenomic studies; Questionnaire Administration
Intervention description: Given SC or IV; Given IV; Correlative studies; Correlative studies; Correlative studies; Correlative studies; Correlative studies; Correlative studies; Correlative studies
Intervention MeSH terms: Rituximab; Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Minimum age: 19 Years
Healthy volunteers: No

Summary:

      RATIONALE: Bortezomib 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 cells to grow and spread. Others find cancer
      cells and help kill them or carry cancer-killing substances to them. Giving bortezomib
      together with rituximab may kill more cancer cells.

      PURPOSE: This phase II trial is studying how well giving bortezomib and rituximab together
      works in treating patients with mantle cell lymphoma who have previously undergone stem cell
      transplantation
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histological documented or cytological confirmed mantle cell
             lymphoma; cyclin D1 must be present as evidenced by either fluorescence in situ
             hybridization (FISH) or immunohistochemical staining

          -  Patients must have undergone autologous hematopoietic stem cell transplantation (AHCT)
             and achieved engraftment by day (D)60-180 as evidenced by absolute neutrophil count
             (ANC) > 1000/mcL and platelets (Plt) > 75,000/mcL

          -  Patients must be in complete remission at D60-180 after AHCT as evidenced by computed
             tomography (CT) scan of the neck/chest/abdomen (abd)/pelvis or CT/positron emission
             tomography (PET) scans

          -  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

          -  Female subject is either post-menopausal or surgically sterilized or willing to use an
             acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine
             device, diaphragm with spermicide, condom with spermicide, or abstinence) for the
             duration of the study

          -  Male subject agrees to use an acceptable method for contraception for the duration of
             the study

          -  Life expectancy of greater than 3 months

          -  Karnofsky > 60%

          -  ANC > 1000/mcL

          -  Plts > 75,000/mcL

          -  Total bilirubin within normal institutional limits, patients with elevation of
             unconjugated bilirubin alone, as in Gilbert's disease, are eligible

          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 2.5 x institutional
             upper limit of normal

          -  Creatinine up to and including 2 mg/dL

        Exclusion Criteria:

          -  Patient has >= grade 2 peripheral neuropathy within 14 days before enrollment and at
             D60-180 after AHCT; patients who had >= grade 2 peripheral neuropathy within 14 days
             before enrollment but resolves to grade 1 or lower peripheral neuropathy at D60-D180
             after AHCT can be enrolled at this time

          -  Patient has > 1.5 x upper limit of normal (ULN) total bilirubin unless history of
             Gilbert's syndrome

          -  Myocardial infarction within 6 months prior to enrollment 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; prior to study entry, any
             electrocardiographic (ECG) abnormality at screening has to be documented by the
             investigator as not medically relevant

          -  Patient has hypersensitivity to bortezomib, boron or mannitol

          -  Female subject is pregnant or breast-feeding; confirmation that the subject is not
             pregnant must be established by a negative serum beta-human chorionic gonadotropin
             (beta-hCG) pregnancy test result obtained during screening; pregnancy testing is not
             required for post-menopausal or surgically sterilized women

          -  Patient has received other investigational drugs with 14 days before treatment of
             treatment with bortezomib + rituximab

          -  Serious medical or psychiatric illness likely to interfere with participation in this
             clinical study

          -  Diagnosed or treated for another malignancy within 3 years of enrollment, 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

          -  Patients with other active malignancies (no evidence of other cancer or life
             expectancy greater than 5 years) are ineligible for this study

          -  Human immunodeficiency virus (HIV) positive patients or hepatitis B or C positive
             patients

          -  Patients with active central nervous system (CNS) disease or history of brain
             metastases (mets) are excluded from study

          -  Prior exposure to either bortezomib or rituximab is not an exclusion criteria