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

LS1081, "A Pilot Study of Dendritic Cell Therapy Delivered Intratumorally After Cryoablation or Intradermally for Patients With B-Cell Non-Hodgkin's Lymphoma"

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 B-cell Non-Hodgkin's lymphoma.

Study Overview

• Status: Completed
• Conditions: Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Splenic Marginal Zone Lymphoma; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Small Lymphocytic Lymphoma; Adult Grade III Lymphomatoid Granulomatosis; Adult Lymphoblastic Lymphoma; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3 Follicular Lymphoma; Adult Diffuse Mixed Cell Lymphoma; Adult Diffuse Small Cleaved Cell Lymphoma; Adult Immunoblastic Large Cell Lymphoma; Waldenstrom Macroglobulinemia With Nodal Disease
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: immunohistochemistry staining method; Other: immunoenzyme technique; Biological: pneumococcal polyvalent vaccine; Biological: dendritic cell vaccine therapy; Procedure: cryotherapy; Biological: autologous dendritic cell-tumor fusion vaccine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histological confirmation of biopsy-proven B-cell non-Hodgkin's lymphoma, excluding chronic lymphocytic leukemia, primary 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Patients receive pneumococcal polyvalent vaccine intramuscularly in weeks -4, 2, and 10. Patients undergo cryoablation followed by dendritic cell vaccine (CA-DC) intratumorally in weeks 0, 2, 4, 6, 10, 14, 18, and 22.	Other: laboratory biomarker analysis; Correlative studies; Other: immunohistochemistry staining method; Correlative studies; Other Names: immunohistochemistry; Other: immunoenzyme technique; Correlative studies; Other Names: immunoenzyme techniques; Biological: pneumococcal polyvalent vaccine; Given intramuscularly; Other Names: Pneumovax 23; Pnu-Imune 23; Biological: dendritic cell vaccine therapy; Given intratumorally; Procedure: cryotherapy; Undergo cryoablation
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, 6, 10, 14, 18, and 22.	Other: laboratory biomarker analysis; Correlative studies; Other: immunohistochemistry staining method; Correlative studies; Other Names: immunohistochemistry; Other: immunoenzyme technique; Correlative studies; Other Names: immunoenzyme techniques; Biological: pneumococcal polyvalent vaccine; Given intramuscularly; Other Names: Pneumovax 23; Pnu-Imune 23; Biological: dendritic cell vaccine therapy; Given intratumorally; Biological: autologous dendritic cell-tumor fusion vaccine; Given intradermally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of significant toxicity as assessed by the CTEP Active Version CTCAE	At day 1 of each course beginning in week 2, every 3 months for 1 year, and during documented progressive disease

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall response rate	At week 4 (arm A) or 2 (arm B) and then every 3 months for 1 year starting at week 10
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	Up to 2.5 years
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	For at least 12 months
Time to response	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
Duration of response	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
Percent change from baseline in index lesion measurements as a marker of distant immune and treatment response	At day 1 of courses 1-4 (arm A) and 1-6 (arm B)
Change in immunologic correlates before and after vaccination treatment	At day 1 of each course beginning in week 2, every 3 months for 1 year, and during documented progressive disease
Correlation of immunologic markers with cancer and treatment-related outcomes (e.g., response, toxicities)	Up to 2.5 years

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Yi Lin, M.D., Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2010
• Primary Completion (Actual): November 24, 2015
• Study Completion (Actual): July 17, 2019

Study Registration Dates

• First Submitted: October 27, 2010
• First Submitted That Met QC Criteria: November 10, 2010
• First Posted (Estimate): November 11, 2010

Study Record Updates

• Last Update Posted (Actual): January 14, 2020
• Last Update Submitted That Met QC Criteria: January 13, 2020
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms, Plasma Cell; Precancerous Conditions; Leukemia, Lymphoid; Leukemia; Leukemia, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma; Lymphoma, Follicular; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma, Mantle-Cell; Lymphoma, B-Cell, Marginal Zone; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Large-Cell, Immunoblastic; Plasmablastic Lymphoma; Waldenstrom Macroglobulinemia; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphomatoid Granulomatosis; Physiological Effects of Drugs; Immunologic Factors; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: LS1081 (Other Identifier: Mayo Clinic Cancer Center & SPORE); NCI-2010-02003 (Registry Identifier: NCI-CTRP); 10-003023 (Other Identifier: Mayo Clinic IRB)