Bortezomib, Cladribine, and Rituximab in Treating Patients With Advanced Mantle Cell Lymphoma or Indolent Lymphoma
Condition: Lymphoma; Mantle Cell Lymphoma; Indolent Lymphoma; SLL
MeSH terms: Lymphoma; Lymphoma, Mantle-Cell
Intervention: rituximab; bortezomib; cladribine
Intervention description: 375 mg/m2 IV Day 1. Repeat every 28 days for a maximum of 6 cycles.; 1.3 mg/m2 IV Days 1 and 4. Repeat every 28 days for a maximum of 6 cycles.; 4 mg/m2 IV over 2 hours Days 1-5. Repeat every 28 days for a maximum of 6 cycles.
Intervention MeSH terms: Rituximab; Bortezomib; Cladribine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: recurrent mantle cell lymphoma; stage III mantle cell lymphoma; stage IV mantle cell lymphoma; recurrent marginal zone lymphoma; stage III marginal zone lymphoma; stage IV marginal zone lymphoma; Waldenstrom macroglobulinemia; recurrent small lymphocytic lymphoma; stage III small lymphocytic lymphoma; stage IV small lymphocytic lymphoma; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage III grade 3 follicular lymphoma; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage IV grade 3 follicular lymphoma; extranodal marginal zone BCL mucosa assoc lymphoid tissue; nodal marginal zone B Cell lymphoma; splenic marginal zone lymphoma

Summary:

      RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes
      needed for cell growth. Drugs used in chemotherapy, such as cladribine, work in different
      ways to stop the growth of cancer cells, either by killing the cells or by stopping them from
      dividing. 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
      cladribine and rituximab may kill more cancer cells.

      PURPOSE: This phase II trial is studying how well giving bortezomib together with cladribine
      and rituximab works in treating patients with advanced mantle cell lymphoma or indolent
      lymphoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Voluntary consent before performance of any study-related procedure

          -  Female subject is either post-menopausal or surgically sterilized or willing to use an
             acceptable method of birth control

          -  Male subject agrees to use an acceptable method for contraception for the duration of
             the study.

          -  Biopsy-proven mantle cell, marginal zone, lymphoplasmacytic, small lymphocytic
             lymphoma, or follicular lymphoma

          -  CD20-positive disease

          -  Patients with marginal zone, lymphoplasmacytic, small lymphocytic, or follicular
             lymphoma - at least one criterion for initiation of treatment must be met:

               -  Symptomatic disease

               -  Cytopenia related to lymphoma

               -  Leukemic phase (> 5,000 malignant lymphocytes/µl)

               -  Mass over 5 cm in greatest diameter

               -  For lymphoplasmacytic lymphoma: additional treatment criteria are serum viscosity
                  ≥ 4 cp, serum monoclonal protein > 5 g/L, concurrent primary systemic AL
                  amyloidosis, cold agglutinin disease

          -  Age over 18

          -  Prior treatment with bortezomib and/or rituximab is acceptable

          -  For follicular lymphoma only, at least one prior treatment

        Exclusion Criteria:

          -  Platelet count of < 100 X10 /L within 14 days before enrollment, unless due to bone
             marrow infiltration with lymphoma, or due to autoimmune thrombocytopenia because of
             lymphoma.

          -  Patient has an absolute neutrophil count of < 1.0 X 10/L within 14 days before
             registration, unless due to bone marrow infiltration with lymphoma.

          -  Patient has a calculated or measured creatinine clearance of <20 mL/minute within 14
             days before registration. (Creatinine Clearance is indicated through the Serum
             Creatinine. If the Serum Creatinine is abnormal, the physician may then due a 24 hour
             urine to further clarify Creatinine Clearance. A 24 hour urine test is not required
             per study.)

          -  Patient has ≥ Grade 2 peripheral neuropathy within 14 days before registration.

          -  Myocardial infarction within 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.

          -  Hypersensitivity to bortezomib, boron or mannitol.

          -  Female subject is pregnant or breast-feeding. Confirmation that the subject is not
             pregnant

          -  Patient received other investigational drugs with 14 days before registration

          -  Serious medical or psychiatric illness likely to interfere with study participation

          -  Diagnosed or treated for another malignancy within 3 years of registration, w/ 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.

          -  CNS involvement with lymphoma.

          -  Known HIV-positive.

          -  History of disease refractory to a purine analog (defined as remission duration of < 6
             months to therapy that included fludarabine, pentostatin, or cladribine).

          -  History of intolerance of bortezomib, boron, mannitol, cladribine, or rituximab.

          -  Patient has > 1.5 X ULN Total Bilirubin

          -  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.