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Phase II Trial to Evaluate an EBV-derived Dendritic Cell Vaccine in Autologous Stem Cell Transplant

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02115126
Recruitment Status : Withdrawn
First Posted : April 15, 2014
Last Update Posted : November 1, 2016
Information provided by (Responsible Party):
David Rizzieri, MD, Duke University

Brief Summary:
This is a non-blinded, not placebo controlled, randomized, parallel phase 2 pilot study to evaluate the immunological response and the safety of Epstein Barr Virus (EBV)-derived tumor antigen, Latent Membrane Protein-2 (LMP2)-loaded dendritic cell (DC) vaccines alone or co-administered with the TLR9 ligand, DUK-CPG-001, in patients with EBV+ lymphoma in the setting of autologous stem cell transplant with infusion of mature T cells. Patients will be randomized to receive vaccine alone or vaccine co-administered with the TLR9 ligand, DUK-CPG-001. Randomization will be stratified by 2 disease types: Hodgkin lymphoma and non-Hodgkin lymphoma.

Condition or disease Intervention/treatment Phase
Hodgkin Lymphoma Non-Hodgkin Lymphoma Biological: LMP2A-loaded conventional DC vaccine Biological: DUK-CPG-001 Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial to Evaluate an EBV Derived Dendritic Cell (DC) Vaccine When Administered Alone or Co-administered With the TLR9 Agonist, DUK-CPG-001, in EBV+ Lymphoma in the Setting of Autologous Stem Cell Transplant
Study Start Date : December 2016
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : January 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Active Comparator: LMP2A-loaded conventional DC vaccine
Epstein-Barr virus (EBV) derived tumor antigen, LMP2 loaded DC vaccine
Biological: LMP2A-loaded conventional DC vaccine

Vaccine #1 will be administered 9-13 weeks status post peripheral blood stem cell (PBSC) infusion. At the time of vaccination, ANC must be > 1.5.

Vaccine #2, the booster vaccine, will be administered 4 weeks +/- 7 days status post vaccine #1. At the time of vaccination, ANC must be > 1.5.

Vaccines will be administered following standard institutional practice for IV infusions using a peripheral or central line and following sterile technique. On the day of vaccination, the patient will be given a total dose of 3 x 107 cells in 30ml of normal saline per vaccination.

Experimental: LMP2A-loaded DC vaccine + DUK-CPG-001
Epstein-Barr virus (EBV) derived tumor antigen, LMP2 loaded DC vaccine co-administered with a Toll-like receptor 9 (TLR9) ligand, DUK-CPG-001
Biological: DUK-CPG-001

On the day of vaccination, for those patients who are randomized to receive DUK-CPG-001, a single vial will be dispensed to the nurse, upon request, by Duke ICS. DUK-CPG-001 will be thawed at room temperature right before use and 0.5 ml (5 mg) will be injected subcutaneously immediately after vaccination.

DUK-CPG-001 will be stored at -20ºC until use. It will be stored in the Duke Investigational Chemotherapy Service pharmacy.

Using standard institutional guidelines and sterile technique for subcutaneous injections, 5 mg of DUK-CPG-001 will be injected subcutaneously immediately after each vaccination.

Primary Outcome Measures :
  1. Immune response [ Time Frame: 7 days post 2nd vaccination ]

    Immune response will be defined as an increase in number of spots to 25-fold more than at baseline, and at least 200 spots per 105 cluster of differentiation 8 (CD8)+ T cells, by Day 7 post 2nd vaccination (i.e., a patient with a baseline of 1 spot/105 CD8+ T cells who achieved 25 spots/million would not be counted as a response).

    "Spots" are the readout for immune activation measured by the enzyme-linked immunosorbent spot (ELISPOT) assay. Each spot is indicative of an activated T cell that secrete interferon (IFN)-gamma, a cytokine produced by activated T cells.

Secondary Outcome Measures :
  1. Number of patients with greater than grade 1 toxicity [ Time Frame: 30 days post last dose of vaccine ]
  2. Duration of the presence of long term memory cells [ Time Frame: 7 days post second dose of vaccine ]
  3. Duration of multi-functional CD8 T cell responses [ Time Frame: 7 days post second dose of vaccine ]
  4. Duration of Th1, Th2 and Th17 cluster of differentiation 4 (CD4) T cell responses as well as CD4+cluster of differentiation 25 (CD25)+Foxp3+ regulatory T cell (Treg) responses [ Time Frame: 7 days post second dose of vaccine ]
  5. Disease free survival [ Time Frame: up to 10 years ]
    Number of days from PBSC transplant until disease relapse or death

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

Each patient must meet all of the following inclusion criteria:

  • Patient must have a histologically proven diagnosis of any EBV+ Hodgkin or non-Hodgkin lymphoma
  • EBV positive will be defined as positive if LMP1 or 2 or EBER are positive. As long as EBV positive on a prior biopsy, EBV testing will not be required at the time of relapse. However, if EBV testing performed on a more recent biopsy and it is negative, that patient will be excluded.
  • Patients must have had persistent, relapsed, or refractory disease to at least one prior regimen with plans to proceed to autologous stem cell transplant
  • Patients must be in a complete remission at time of initial pheresis for vaccine preparation; complete remission will be determined using Cheson Criteria100
  • There are no limits on the number of prior therapies allowed
  • Able to give voluntary written informed consent
  • Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study therapy and for 3 months after vaccine #2.
  • Male subject agrees to use an acceptable method for contraception for the duration of the study therapy and for 3 months after vaccine #2.
  • Patients must be 18 years of age or older.
  • ECOG performance status 0-2.

Exclusion Criteria

  • An estimated or measured creatinine clearance of less than 30 ml/min.
  • AST, ALT, total bilirubin > 3 times the upper limit of normal
  • Patients on chronic immunosuppressive therapy for any reason (other than chemotherapy for HL)
  • Chronic systemic steroid therapy at doses greater than 10mg/day of prednisone or its equivalent.
  • Female subject is pregnant or lactating. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result within 48 hours of enrollment. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
  • Patient has received other investigational drugs for this disease within 14 days of enrollment
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
  • Patients who are HIV positive AND have a CD4 count <50
  • Prior solid organ transplant or allogeneic stem cell transplant

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02115126

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United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
David Rizzieri, MD
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Principal Investigator: Anne Beaven, MD Duke University

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Responsible Party: David Rizzieri, MD, Professor of Medicine, Duke University Identifier: NCT02115126     History of Changes
Other Study ID Numbers: Pro00042574
First Posted: April 15, 2014    Key Record Dates
Last Update Posted: November 1, 2016
Last Verified: October 2016

Additional relevant MeSH terms:
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Lymphoma, Non-Hodgkin
Hodgkin Disease
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Immunologic Factors
Physiological Effects of Drugs