Bortezomib, Cladribine, and Rituximab in Treating Patients With Advanced Mantle Cell Lymphoma or Indolent Lymphoma (VCR)

This is an interventional treatment trial for Lymphoma focused on measuring 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 Read More

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.