Clinical Trials /

A Pilot Study of a Personalized Neoantigen Cancer Vaccine Following Front-Line Rituximab in Follicular Lymphoma

NCT03361852

Description:

This research study is studying a novel type of FL vaccine as a possible treatment for follicular lymphoma (FL). The agents involved in this study are: - Personalized NeoAntigen vaccine - Poly-ICLC

Related Conditions:
  • Follicular Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Pilot Study of a Personalized Neoantigen Cancer Vaccine Following Front-Line Rituximab in Follicular Lymphoma
  • Official Title: A Pilot Study of a Personalized Neoantigen Cancer Vaccine Following Front-Line Rituximab in Follicular Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: 17-353
  • NCT ID: NCT03361852

Conditions

  • Follicular Lymphoma

Interventions

DrugSynonymsArms
RituximabRituxanNeo Vax
Neo VaxNeo Vax

Purpose

This research study is studying a novel type of FL vaccine as a possible treatment for follicular lymphoma (FL). The agents involved in this study are: - Personalized NeoAntigen vaccine - Poly-ICLC

Detailed Description

      This research study is a Pilot Study, which is the first time investigators are examining the
      Personalized Neoantigen Vaccine (NeoVax) in patients diagnosed with follicular lymphoma. The
      FDA (the U.S. Food and Drug Administration) has not approved the Personalized Neoantigen
      Vaccine as a treatment for any disease.

      The purpose of this study is to determine if it is possible to make and safely administer a
      vaccine against FL by using information gained from specific genetic characteristics of the
      participant own FL. The investigators plan to analyze the specific genetic characteristics of
      the participant own FL (mutations) and use that information to produce proteins that may help
      the participant's immune system recognize and fight FL cells.

      This vaccine is also being tested in clinical trials in patients with advanced melanoma (a
      type of skin cancer) or glioblastoma (a type of brain cancer). The current study will examine
      the ability of the vaccine to stimulate the participant's immune system when given at several
      different timepoints, and will examine the participant's blood cells for signs that the FL
      has changed or decreased.

      FL cells will be obtained from lymph node biopsy, blood draws or effusion. The genetic
      material contained in the FL cells will be examined for the presence of tumor-specific
      mutations. This information will be used to prepare small protein fragments, which are called
      "peptides." The vaccine will consist of up to 20 of these peptides as well as a drug called
      Poly-ICLC. A peptide from the tetanus vaccine will also be included to boost the immune
      response.

      Poly-ICLC (also called Hiltonol) is an experimental "viral mimic" and an activator of
      immunity. Poly-ICLC binds proteins on the surface of certain immune cells to make it appear
      as if a virus is present. When the cells detect the vaccine, they think it is a virus and
      turn on the immune system. Poly-ICLC will be mixed with NeoAntigen peptides and administered
      as an injection given underneath the skin. Poly-ICLC is an investigational drug, meaning the
      FDA has not approved it as a treatment for any disease.
    

Trial Arms

NameTypeDescriptionInterventions
Neo VaxExperimentalNeo Vax is injected into up to 4 different anatomic site. NeoVax may be administered within +/- 1 day of the scheduled administration date for days 4 and 8, Within +/-3 days of the scheduled administration date for days 15 and 22 Within +/-7 days of days 78 and 134. Participants will receive Rituximab weekly x 4 weeks per institutional standard
  • Rituximab
  • Neo Vax

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnosis of grade I-IIIA follicular lymphoma (pathology must be confirmed at
             DFCI/BWH)

          -  Planned treatment with 4 weekly doses of rituximab.

          -  No prior systemic therapy for follicular lymphoma; prior radiation with palliative or
             curative intent is allowed if radiation occurred more than 3 months prior to study
             entry

          -  Patient must have measurable disease by Cheson criteria

          -  Age ≥ 18 years.

          -  ECOG performance status < 2.

          -  Participants must have normal organ and marrow function as defined below:

               -  total bilirubin less than institutional ULN (<1.5 x ULN if patient has a history
                  of Gilbert's disease

               -  AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal

               -  ANC >500 (for secondary screening only)

               -  Platelet count >75,000 (for secondary screening only)

          -  The effects of NeoVax and poly-ICLC on the developing human fetus are unknown. For
             this reason, women of childbearing potential (WOCBP) must have a negative pregnancy
             test (serum) before entry onto the trial and within 7 days prior to start of study
             vaccination.

          -  Female patients enrolled in the study, who are not free from menses for >2 years, post
             hysterectomy / oophorectomy, or surgically sterilized, must be willing to use either 2
             adequate barrier methods or a barrier method plus a hormonal method of contraception
             to prevent pregnancy or to abstain from sexual activity throughout the study, starting
             with visit 1 through 4 weeks after the last dose of study therapy. Approved
             contraceptive methods include for example; intra uterine device, diaphragm with
             spermicide, cervical cap with spermicide, male condoms, or female condom with
             spermicide. Spermicides alone are not an acceptable method of contraception. Male
             participants need to agree to use an adequate method of contraception

          -  Patient is agreeable to allow tumor (from peripheral blood, lymph node, or effusion)
             and normal tissue (from saliva) samples to be submitted for complete exome and
             transcriptome sequencing.

          -  Ability to understand and the willingness to sign a written informed consent document.

          -  Additional Inclusion Criteria for Treatment Registration

          -  Participants must meet the following criteria (in addition to the above) to be
             eligible to proceed to receive vaccine treatment on the study:

          -  At least 7 immunizing peptides can be designed

          -  Continue to meet inclusion and exclusion criteria for Screening Registration (note:
             hepatitis B and hepatitis C serologies do not need to be repeated unless there is a
             clinical concern that an exposure has occurred since the screening phase).

          -  Achieved a CR, PR, or SD with no residual mass greater than 5 cm per Lugano criteria
             following single agent rituximab per

        Exclusion Criteria:

          -  Prior systemic therapy for follicular lymphoma with the exception of 4 weekly doses of
             rituximab as proscribed per protocol

          -  Radiation with palliative or curative intent within 90 days of study screening

          -  Participants who are receiving any other investigational agents.

          -  Previous bone marrow or stem cell transplant

          -  Concomitant therapy with immunosuppressive or immunomodulatory agents; chronic use of
             systemic corticosteroids at doses of 10 mg of prednisone (or equivalent) for
             indications other than treatment of follicular lymphoma is acceptable. Use of higher
             doses of corticosteroids after initial registration is acceptable if tapered to 10 mg
             of prednisone (or equivalent) or les at least 7 days prior to NeoVax administration so
             long as the corticosteroids were not administered for follicular lymphoma.

          -  Use of a non-oncology vaccine therapy for prevention of infectious diseases within 2
             weeks prior to any NeoVax administration.

          -  History of severe allergic reactions attributed to any vaccine therapy for the
             prevention of infectious diseases.

          -  Active, known, or suspected autoimmune disease or immunosuppressive conditions with
             the exception of vitiligo, type 1 diabetes, residual autoimmune-related hypothyroidism
             requiring hormone replacement, or psoriasis not requiring systemic treatment.

          -  Progressive disease or stable disease with residual tumor mass > 5 cm by CT scan
             (measured as long axis) following 4 weekly doses of rituximab (for treatment phase
             only).

          -  Any documented transformation to diffuse large B cell lymphoma or grade 3Bfollicular
             lymphoma.

          -  Currently requiring chronic intravenous immunoglobulin G (IVIG)

          -  Active infection with hepatitis B or C (see Study Calendar in Section 10 for screening
             assays).

          -  Uncontrolled intercurrent illness including, but not limited to ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia.

          -  Any underlying medical condition, psychiatric condition or social situation that in
             the opinion of the investigator would compromise study administration as per protocol
             or compromise the assessment of AEs.

          -  Pregnant women are excluded from this study because personalized neoantigen peptides
             and poly-ICLC are agents with unknown risks to the developing fetus. Because there is
             an unknown but potential risk of adverse events in nursing infants secondary to
             treatment of the mother with personalized neoantigen peptides and poly-ICLC, nursing
             women are excluded from this study.

          -  Individuals with history of an invasive malignancy are ineligible except for the
             following circumstances: a) individuals with a history of invasive malignancy are
             eligible if they have been disease -free for at least 3 years and are deemed by the
             investigator to be at low risk for recurrence of that malignancy; b) individuals with
             the following cancers are eligible if diagnosed and treated: carcinoma in situ of the
             breast, oral cavity or cervix and basal cell or squamous cell carcinoma of the skin;
             c) individuals with prostate cancer managed with active surveillance that is not
             expected to limit their survival to <10 years.

          -  Participants with known CNS involvement

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to poly-ICLC.

          -  HIV-positive participants including those on combination antiretroviral therapy are
             ineligible because assessment of immunologic endpoints may be confounded by
             HIV-induced alterations in patient immune status and functio
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Feasibility of Neovax following 4 weekly doses of rituximab assessed by the following
Time Frame:2 years
Safety Issue:
Description:The proportion of all enrolled patients for whom sequencing and analysis leads to identification of at least 7 actionable peptides to initiate vaccine production and, of the patients who generate at least 7 actionable peptides, the proportion for whom the time from sample collection to vaccine availability is less than 12 weeks.

Secondary Outcome Measures

Measure:The proportion of participants who achieve an IFN-γ T cell response to one or more of the peptide pools
Time Frame:2 years
Safety Issue:
Description:The induction of IFN-γ T-cell response will be based on ELISPOT assessments taken prior to vaccine administration and at week 16 from both peripheral blood draws and bone marrow biopsies. The proportion of patients who achieve more than 55 SFU/106 PBMC or 3 times their baseline level will be presented with a 90% exact binomial confidence interval. Based on a cohort of size 10, the confidence interval will be no wider than 0.55. It is possible that the maximal response will occur at a different sampling time point or will vary between participants. Thus, this time point may vary from week 16.
Measure:The proportion of participants who convert from PR to CR
Time Frame:2 years
Safety Issue:
Description:The investigators will report the proportion of patients converting from SD to CR/PR or from PR to CR based upon Lugano criteria in a descriptive fashion.
Measure:The proportion of participants who convert from SD to PR/CR
Time Frame:2 years
Safety Issue:
Description:The investigators will report the proportion of patients converting from SD to CR/PR or from SD to PR or CR based upon Lugano criteria in a descriptive fashion.
Measure:Best Objective Response
Time Frame:2 years
Safety Issue:
Description:The investigators will report the best objective response (CR, PR, SD, or PD) based upon Lugano criteria in a descriptive fashion.
Measure:To describe the safety and tolerability of NeoVax following 4 weekly doses of rituximab in patient with previously untreated follicular lymphoma
Time Frame:2 years
Safety Issue:
Description:The investigators will report toxicity in a descriptive fashion using CTCAE version 4.0

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Follicular Lymphoma

Last Updated

June 21, 2019