Clinical Trials /

Ovarian Dendritic Cell Vaccine Trial

NCT00703105

Description:

The purpose of this study is to determine if a dendritic cell vaccine made with autologous tumor lysate or for patients who are HLA-A2 with peptides of MUC1 and WT1 therapy will produce remissions in patients with advanced ovarian cancer. This research is being done because we want to find new therapies for treatment of relapsed or refractory (resistant to ordinary treatment) ovarian cancer. The use of vaccine therapy is research. A new experimental approach for treating refractory or relapsed ovarian cancer involves using the patients own immune system to kill the cancer cells. These immune cells are called monocytes and are harvested from blood. The process of Leukapheresis collects the monocytes called Dendritic Cells. This is usually a 3 hour process done in the comfort of a hospital bed in the apheresis lab, similar to giving blood for donation. Approximately 300cc's are collected during this process, the equivalent of about 10 ounces of blood. Once these dendritic cells are collected - a special laboratory grows and processes them into a vaccine using a patient's own tumor cells or for those with a specific HLA type (HLA-A2) with tumor peptides. This preparation is then given back to the patient hopefully to stimulate the immune system to kill cancer cells. This type of treatment is considered biological research.

Related Conditions:
  • Ovarian Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ovarian Dendritic Cell Vaccine Trial
  • Official Title: Defining the Role of CD4+CD25+ Immunoregulatory T-cells in the Treatment of Patients With Advanced Ovarian Cancer Who Receive Dendritic Cell Based Vaccine Therapies

Clinical Trial IDs

  • ORG STUDY ID: 200541
  • NCT ID: NCT00703105

Conditions

  • Ovarian Cancer

Interventions

DrugSynonymsArms
DC vaccinationAutologous Dendritic Cell Vaccination

Purpose

The purpose of this study is to determine if a dendritic cell vaccine made with autologous tumor lysate or for patients who are HLA-A2 with peptides of MUC1 and WT1 therapy will produce remissions in patients with advanced ovarian cancer. This research is being done because we want to find new therapies for treatment of relapsed or refractory (resistant to ordinary treatment) ovarian cancer. The use of vaccine therapy is research. A new experimental approach for treating refractory or relapsed ovarian cancer involves using the patients own immune system to kill the cancer cells. These immune cells are called monocytes and are harvested from blood. The process of Leukapheresis collects the monocytes called Dendritic Cells. This is usually a 3 hour process done in the comfort of a hospital bed in the apheresis lab, similar to giving blood for donation. Approximately 300cc's are collected during this process, the equivalent of about 10 ounces of blood. Once these dendritic cells are collected - a special laboratory grows and processes them into a vaccine using a patient's own tumor cells or for those with a specific HLA type (HLA-A2) with tumor peptides. This preparation is then given back to the patient hopefully to stimulate the immune system to kill cancer cells. This type of treatment is considered biological research.

Detailed Description

      Patients with advanced ovarian carcinoma who have failed initial curative chemotherapy
      attempts will be evaluated at the time of relapse for tumor debulking surgery prior to the
      initiation of salvage chemotherapy. If appropriate, samples will be collected for tumor
      lysate preparation for vaccination as per the existing Loyola protocol. Lysates may also be
      produced by the collection of malignant effusions as performed for palliation of symptoms.
      Patients will then receive palliative chemotherapy to a maximum tumor cytoreduction. Patients
      from whom sufficient tumor cells have been collected for DC-based vaccine production will
      undergo a leukapheresis for DC cell production. Once completed, these patients will receive a
      DC vaccination with 1 x 106 tumor lysate and KLH-loaded immature DCs into inguinal nodes
      identified by ultrasound guidance for a total of three injections at two week intervals; or
      for those who are HLA-A2 restricted with pharmaceutical grade MUC1 and WT1 tumor peptides.
    

Trial Arms

NameTypeDescriptionInterventions
Autologous Dendritic Cell VaccinationExperimentalDC vaccination with 1 x 10(6th) tumor lysate or WT1 and MUC1 peptide and KLH-loaded immature DCs into inguinal nodes identified by ultrasound guidance for a total of three injections at two week intervals(6 weeks)
  • DC vaccination

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have a histologic or cytologic diagnosis of epithelial ovarian cancer

          -  Patients are eligible if they have failed to enter a complete remission with induction
             therapy or have relapsed after a period of remission and are not eligible for
             otherwise curative therapy

          -  Patients must not have received any antineoplastic chemotherapy or immunotherapy for
             the four weeks preceding tumor excision; six weeks for nitrosoureas and mitomycin-C

          -  Patients must not have received irradiation for the four weeks prior to removal of the
             tumor and no previously irradiated tumor deposits may be used for tumor lysate in the
             development of the dendritic cell vaccine

          -  Age >18 years. Because no dosing or adverse event data are currently available on the
             use of Ontak in combination with dendritic cell vaccination in patients <18 years of
             age, children are excluded from this study but may be eligible for future pediatric
             phase 2 combination trials

          -  Life expectancy of greater than three months

          -  Karnofsky performance status must be >70%; (see appendix A)

          -  Patients must have adequate baseline hematopoetic function as defined below. - The
             following labs must be drawn within four weeks of having the tumor harvested and/or
             receiving the dose of Ontak

               -  total white blood cell count > 2,500/mm3

               -  absolute neutrophil count > 1,000/mm3

               -  absolute lymphocyte count > 500/mm3

               -  platelet count > 80,000/mm3

          -  Patients must have adequate baseline organ function as defined below. The following
             labs must be drawn within four weeks of having the tumor harvested and/or receiving
             the dose of Ontak:

               -  total bilirubin ≤ 2.0 mg/dl

               -  AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal

               -  creatinine ≤2.0 mg/dl

               -  prothrombin time (INR) ≤1.5 X institutional upper limit of normal

               -  albumin >3.0 mg/dl

          -  If patients have had recent surgery, then they must be fully recovered from the
             effects of that surgery.

          -  The effects of Ontak on the developing human fetus at the recommended therapeutic dose
             are unknown. Women of child-bearing potential must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for
             the duration of study participation. Should a woman become pregnant or suspect she is
             pregnant while participating in this study, she should inform her treating physician
             immediately.

          -  Patients must have the ability to understand and the willingness to sign a written
             informed consent document.

        Additional eligibility requirements for vaccine therapy initiation:

          -  Patients are eligible after tumor collection for the vaccine strategy, or for those
             selected to receive ONTAK alone (group 3) because tumor is not available can enroll at
             ay time they fulfill the Eligibility Criteria. Pre-vaccination the goal is to
             establish a Minimal Residual Disease state (MRD maximum tumor diameter of any residual
             disease ≤ 1cm). This can be achieved with surgery and/or salvage chemotherapy. Ontak
             administration and/or vaccine therapy will commence at least 4 weeks after the
             completion of the last day of any of the aforementioned therapies

          -  Patients to be randomized to groups 1 and 2 must have tumor available for preparation
             of tumor lysate vaccine

          -  Women and members of all races and ethnic groups are eligible for this trial

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to entering the study or those who have not
             recovered from adverse events due to agents administered more than 4 weeks earlier

          -  Patients may not be receiving any other investigational agents.

          -  Patients who have received prior anti-tumor vaccines are ineligible

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to monocolonal antibodies from Murine sources

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, active bleeding, symptomatic congestive heart failure, unstable angina
             pectoris, cardiac arrhythmia, uncontrolled bronchospasm, hypertension, hyperglycemia,
             or hypercalcemia; or psychiatric illness/social situations that in the opinion of the
             investigators would compromise the patient's ability to tolerate this treatment or
             affect compliance

          -  Pregnant and lactating women are excluded from this study. Because there is an unknown
             but potential risk for adverse events in nursing infants, breastfeeding should be
             discontinued if the mother is treated with Ontak. These potential risks may also apply
             to other agents used in this study

          -  Patients with HIV infection, AIDS, or hepatitis B surface antigen positivity, are
             excluded from this trial. Patients on combination antiretroviral therapy are
             ineligible because of the potential for pharmacokinetic interactions. In addition,
             these patients are at increased risk of lethal infections when treated with
             marrow-suppressive therapy

          -  History of corticosteroid use in the four weeks preceding entry onto the clinical
             trial, or the requirement for ongoing corticosteroid use during the study period

          -  Patients who are expected to require therapeutic anticoagulation during the trial
             period

          -  Patients with known brain metastases
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:To determine if administration of an autologous tumor lysate or tumor peptide-loaded dendritic cell vaccine enhances the immune response in patients with relapsed/refractory ovarian cancer
Time Frame:days 45 and 62 post vaccine
Safety Issue:
Description:response rate

Secondary Outcome Measures

Measure:To characterize the toxicities of this novel DC-based vaccination strategy.
Time Frame:weekly assessments for a total of 4 weeks
Safety Issue:
Description:CTAE4 toxicities

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Loyola University

Trial Keywords

  • ovarian cancer
  • Tregs
  • vaccine
  • Recurrent Ovarian Cancer

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