Vaccine Therapy With or Without Cryosurgery in Treating Patients With Residual, Relapsed, or Refractory B-Cell Non-Hodgkin Lymphoma

• Overall response rate [ Time Frame: At week 4 (arm A) or 2 (arm B) and then every 3 months for 1 year starting at week 10 ] [ Designated as safety issue: No ]
• Feasibility as estimated by the number of patients receiving at least one dose of tumor antigen loading and vaccine delivery divided by the number receiving leukapheresis [ Time Frame: Up to 2.5 years ] [ Designated as safety issue: No ]
• Clinical benefit rate as estimated by the number of patients with an objective status of stable disease (SD) or an objective status of CR or PR [ Time Frame: For at least 12 months ] [ Designated as safety issue: No ]
• Time to response [ Time Frame: From the date of initiation of vaccination treatment to the date at which the patient's objective status is first noted to be either a CR or PR ] [ Designated as safety issue: No ]
• Duration of response [ Time Frame: From the date at which the patient's objective status is first noted to be either a CR or PR to the earliest date progression is documented ] [ Designated as safety issue: No ]
• Percent change from baseline in index lesion measurements as a marker of distant immune and treatment response [ Time Frame: At day 1 of courses 1-4 (arm A) and 1-6 (arm B) ] [ Designated as safety issue: No ]
• Change in immunologic correlates before and after vaccination treatment [ Time Frame: At day 1 of each course beginning in week 2, every 3 months for 1 year, and during documented progressive disease ] [ Designated as safety issue: No ]
• Correlation of immunologic markers with cancer and treatment-related outcomes (e.g., response, toxicities) [ Time Frame: Up to 2.5 years ] [ Designated as safety issue: No ]

RATIONALE: Vaccines, such as dendritic cell therapy (DC) made from a person's tumor cells and white blood cells may help the body build an effective immune response to kill tumor cells. Cryosurgery kills cancer cells by freezing them. Giving vaccine therapy together with cryosurgery may kill more tumor cells. PURPOSE: This clinical trial studies giving vaccine therapy together with or without cryosurgery in treating patients with residual, relapsed, or refractory B-cell Non-Hodgkin's lymphoma.

PRIMARY OBJECTIVES: I. Evaluation of safety and tolerability as measured by the incidence of significant toxicity of an autologous DC vaccine injection into a cryoablated tumor site (Arm A). II. Evaluation of safety and tolerability as measured by the incidence of significant toxicity of an autologous mature DC vaccine + tumor lysate generated in vitro and delivered intradermally (ID) (Arm B). SECONDARY OBJECTIVES: I. For cryoablation candidates: To assess feasibility, overall response rate, clinical benefit rate, time to response, and duration of response (Arm A). II. For patients receiving ID vaccine without cryoablation: To assess feasibility, clinical response rate, time to response, and duration of response (Arm B). TERTIARY OBJECTIVES: I. For cryoablation candidates: To assess the change over time in non-cryoablated nodes selected as the index lesions (Arm A). II. For patients receiving ID vaccine without cryoablation: To assess the change over time in measurable nodes selected as the index lesions (Arm B). III. To monitor patients' immune response after vaccine therapy. IV. Assess the immune response to Prevnar in cancer patients. V. Assess the effect of DC vaccination on presence of myeloid suppressors. VI. Assess the effect of tumor antigen delivery methods (in vivo DC into cryoablated tumor vs. ID injection of in vitro generated DC + lysate) on T cell response. OUTLINE: Patients are assigned to 1 of 2 treatment arms. In both arms, treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year, and then every 6 months for up to 2.5 years.

• Cutaneous B-cell Non-Hodgkin Lymphoma
• Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
• Intraocular Lymphoma
• Nodal Marginal Zone B-cell Lymphoma
• Recurrent Adult Diffuse Large Cell Lymphoma
• Recurrent Adult Diffuse Mixed Cell Lymphoma
• Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
• Recurrent Adult Grade III Lymphomatoid Granulomatosis
• Recurrent Adult Immunoblastic Large Cell Lymphoma
• Recurrent Adult Lymphoblastic Lymphoma
• Recurrent Grade 1 Follicular Lymphoma
• Recurrent Grade 2 Follicular Lymphoma
• Recurrent Grade 3 Follicular Lymphoma
• Recurrent Mantle Cell Lymphoma
• Recurrent Marginal Zone Lymphoma
• Recurrent Small Lymphocytic Lymphoma
• Splenic Marginal Zone Lymphoma
• Waldenstrom Macroglobulinemia

• Biological: dendritic cell vaccine therapy
  Given intratumorally
• Procedure: cryotherapy
  Undergo cryoablation
• Biological: pneumococcal polyvalent vaccine
  Given intramuscularly
  Other Names:

  • Pneumovax 23
  • Pnu-Imune 23
• Other: laboratory biomarker analysis
  Correlative studies
• Other: immunoenzyme technique
  Correlative studies
  Other Name: immunoenzyme techniques
• Other: immunohistochemistry staining method
  Correlative studies
  Other Name: immunohistochemistry
• Biological: autologous dendritic cell-tumor fusion vaccine
  Given intradermally

• Experimental: Arm A
  Patients receive pneumococcal polyvalent vaccine intramuscularly in weeks -4 and 2. Patients undergo cryoablation followed by dendritic cell vaccine (CA-DC) intratumorally in weeks 0 and 2.
  Interventions:

  • Biological: dendritic cell vaccine therapy
  • Procedure: cryotherapy
  • Biological: pneumococcal polyvalent vaccine
  • Other: laboratory biomarker analysis
  • Other: immunoenzyme technique
  • Other: immunohistochemistry staining method
• Experimental: Arm B
  Patients receive pneumococcal polyvalent vaccine as in arm A. Patients also receive autologous dendritic cell-tumor fusion vaccine (TL-DC) intradermally in weeks 0, 2, 4, and 6.
  Interventions:

  • Biological: pneumococcal polyvalent vaccine
  • Other: laboratory biomarker analysis
  • Other: immunoenzyme technique
  • Other: immunohistochemistry staining method
  • Biological: autologous dendritic cell-tumor fusion vaccine

Inclusion Criteria:

• Histological confirmation of biopsy-proven residual, relapsed, or refractory B-cell non-Hodgkin's lymphoma, excluding chronic lymphocytic leukemia/small lymphocytic lymphoma, primary central nervous system (CNS) lymphoma and Burkitt's lymphoma
• Patient must have at least 2 measurable lesions that are >= 1.5cm in one dimension. One of the lesions, must meet additional criteria a or b depending on the treatment arm. a) For Arm A, patient must have at least one lesion that is >= 2.0cm and is amenable to image-guided cryoablation and multiple vaccine injections as determined by Interventional Radiology (including tumors that can be safely accessed using imaging guidance and treated with minimal risk to adjacent structures). b) For Arm B, patient must have one lesion that can be excised for in vitro vaccine preparation.
• ECOG Performance Status (PS) 0, 1, 2
• Absolute neutrophil count > 1000/uL
• Absolute lymphocyte count > 500/uL
• PLT >= 100,000/uL
• HgB >= 8.0 g/dL
• Total bilirubin =< 1.5 x upper limit of normal (ULN) or if total bilirubin is > 1.5 x ULN, the direct bilirubin must be normal
• Negative serum pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
• Provide informed written consent
• Willingness to return to a Lymphoma SPORE enrolling institution for follow-up
• Patient willing to provide tissue and blood samples for research purposes

Exclusion Criteria:

• Pregnant women
• Nursing women
• 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 toxicity of the prescribed regimens
• Patients known to be HIV positive
• Serious non-malignant disease such as active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations or other conditions which in the opinion of the investigator would compromise protocol objectives
• Receiving any other investigational agent considered as a treatment for the primary neoplasm
• History of other primary malignancy requiring systemic treatment within 6 months of protocol enrollment
• Patients must not have another active malignancy requiring treatment
• Patients must not be receiving chemotherapy or immunotherapy for another cancer
• Prior allogeneic bone marrow or peripheral blood stem cell transplantation
• Prior autologous bone marrow or peripheral blood stem cell support within 1 year
• Major surgery other than diagnostic surgery =< 4 weeks
• History of hypersensitivity and anaphylactoid reactions to pneumococcal vaccine or any component of the formulation, including diphtheria toxoid
• Active autoimmune disease such as Crohn's disease, rheumatoid arthritis, Sjogrens' disease, systemic lupus erythematosis, or similar conditions
• Coagulopathy, including the use of Coumadin or heparin anticoagulants that cannot be discontinued for the cryoablation procedure (NOTE: Heparin for line patency without detectable lab abnormalities for coagulation will be allowed)
• Patients must be off corticosteroids for at least 2 weeks prior to registration (this includes oral, IV, subcutaneous, or inhaled route of administration); patients on chronic corticosteroid for adrenal insufficiency or other reasons may enroll if they receive less than 10 mg/day of prednisone (or equivalent)
• Patients with active CNS malignancy are not eligible for this trial