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

NCT02115126 | Withdrawn Phase 2

• 1 other identifier: Pro00042574
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Hodgkin Lymphoma; Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Immune response

  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.

  7 days post 2nd vaccination

Secondary Outcomes (5)

• Number of patients with greater than grade 1 toxicity

  30 days post last dose of vaccine

• Duration of the presence of long term memory cells

  7 days post second dose of vaccine

• Duration of multi-functional CD8 T cell responses

  7 days post second dose of vaccine

• 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

  7 days post second dose of vaccine

• Disease free survival

  up to 10 years

Study Arms (2)

LMP2A-loaded conventional DC vaccine

ACTIVE COMPARATOR

Epstein-Barr virus (EBV) derived tumor antigen, LMP2 loaded DC vaccine

Biological: LMP2A-loaded conventional DC vaccine

LMP2A-loaded DC vaccine + DUK-CPG-001

EXPERIMENTAL

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

Interventions

LMP2A-loaded conventional DC vaccine BIOLOGICAL

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.

LMP2A-loaded conventional DC vaccine

DUK-CPG-001 BIOLOGICAL

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.

LMP2A-loaded DC vaccine + DUK-CPG-001

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• David Rizzieri, MD: lead

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Hodgkin Disease; Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Anne Beaven, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: April 8, 2014
• First Posted: April 15, 2014
• Study Start: December 1, 2016
• Primary Completion: January 1, 2020
• Study Completion: January 1, 2025
• Last Updated: November 1, 2016

Record last verified: 2016-10

Locations

US (1)