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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01239875
First received: October 27, 2010
Last updated: September 12, 2014
Last verified: September 2014
  Purpose

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.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: LS1081, "A Pilot Study of Dendritic Cell Therapy Delivered Intratumorally After Cryoablation or Intradermally for Patients With B-Cell Non-Hodgkin's Lymphoma"

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Incidence of significant toxicity as assessed by the CTEP Active Version CTCAE [ 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: Yes ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 26
Study Start Date: November 2010
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
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.
Biological: dendritic cell vaccine therapy
Given intratumorally
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01239875

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Study Chair: Yi Lin, M.D. Mayo Clinic
  More Information

No publications provided

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT01239875     History of Changes
Other Study ID Numbers: LS1081, NCI-2010-02003, LS1081, 10-003023
Study First Received: October 27, 2010
Last Updated: September 12, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphoma, Mantle-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, B-Cell
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Large-Cell, Immunoblastic
Lymphoma
Waldenstrom Macroglobulinemia
Lymphoma, Extranodal NK-T-Cell
Lymphomatoid Granulomatosis
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Leukemia, Lymphoid
Leukemia
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoma, T-Cell
Precancerous Conditions

ClinicalTrials.gov processed this record on October 01, 2014