Ovarian Dendritic Cell Vaccine Trial

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Loyola University
Sponsor:
Information provided by (Responsible Party):
Patrick Stiff, Loyola University
ClinicalTrials.gov Identifier:
NCT00703105
First received: June 19, 2008
Last updated: June 5, 2014
Last verified: June 2014
  Purpose

The purpose of this study is to determine if an immune modifying drug (Ontak) alone or as part of a vaccine 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 ONTAK and 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. 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.

This study also involves a drug called ONTAK, which is made using certain proteins from diphtheria toxins and interleukin-2 (chemotherapy drug). This drug will act on immune suppressing cells normally present in your body making vaccine therapy possibly less effective. Ontak helps set up your immune system to be boosted by the vaccine injections. The use of Ontak followed by the vaccine to stimulate your tumor killing immune cells has not been done in ovarian cancer before and is research.


Condition Intervention Phase
Ovarian Cancer
Biological: Ontak DC
Biological: DC vaccination
Drug: Ontak
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Loyola University:

Primary Outcome Measures:
  • To determine if immunoregulatory T-cell inhibition by Ontak followed by the administration of an autologous tumor lysate-loaded dendritic cell vaccine enhances the immune response in patients with relapsed/refractory ovarian cancer [ Time Frame: days 45 and 62 post vaccine ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To define the in vitro and in vivo responses of Ontak with and without DC vaccination. [ Time Frame: Days 46 and 62 post vaccine ] [ Designated as safety issue: No ]
  • To characterize the toxicities of this novel Treg/DC-based vaccination strategy. [ Time Frame: weekly assessments for a total of 4 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 36
Study Start Date: October 2008
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Administration of a single dose of Ontak at 18 µg/kg followed in 96 hours by DC vaccination with 1 x 10(6th) tumor lysate and KLH-loaded immature DCs into inguinal nodes identified by ultrasound guidance for a total of three injections at two week intervals (6 weeks)
Biological: Ontak DC
Administration of a single dose of Ontak at 18 µg/kg followed in 96 hours by DC vaccination with 1 x 10(6th) tumor lysate and KLH-loaded immature DCs into inguinal nodes identified by ultrasound guidance for a total of three injections at two week intervals (6 weeks)
Other Name: denileukin diftitox (Ontak)
Experimental: 2
DC vaccination with 1 x 10(6th) tumor lysate and KLH-loaded immature DCs into inguinal nodes identified by ultrasound guidance for a total of three injections at two week intervals(6 weeks)
Biological: DC vaccination
DC vaccination with 1 x 10(6th) tumor lysate and KLH-loaded immature DCs into inguinal nodes identified by ultrasound guidance for a total of three injections at two week intervals; (6 weeks)
Experimental: 3
administration of Ontak ,18 µg/kg at the same dose without vaccination.
Drug: Ontak
administration of Ontak 18 µg/kg without vaccination
Other Name: denileukin diftitox

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 be randomly assigned one of two treatment groups: Cohort (Group) 1 - Administration of a single dose of Ontak at 18 μg/kg followed by 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 Cohort (Group) 2 - Identical DC vaccination as in Group 1 without Ontak pre-treatment. Patients for whom collection of tumor cells for lysate preparation is not possible will be assigned to Cohort (Group) 3, with administration of Ontak at the same dose without vaccination. In this pilot study we plan to treat 12 patients in each group over a two-year period of time. Therapy will begin four weeks after chemotherapy completion, given to achieve maximum cytoreduction prior to protocol therapy initiation

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  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: NCT00703105

Contacts
Contact: Sandra Zakrzewski, RN 708-327-2831 SZAKRZE@lumc.edu

Locations
United States, Illinois
Loyola Univeristy Medical Center, Cardinal Bernardin Cancer Center Recruiting
Maywood, Illinois, United States, 60153
Sub-Investigator: Brian Nickoloff, MD PhD         
Sub-Investigator: Cheryl Czerlanis, MD         
Sub-Investigator: Ronald Potkul, MD         
Sub-Investigator: Donna Smith, MD         
Sub-Investigator: Margo Shoup, MD         
Sub-Investigator: Amir Elmishad, MD         
Sub-Investigator: Alia Salhadar, MD         
Sponsors and Collaborators
Loyola University
Investigators
Principal Investigator: Patrick Stiff, MD Loyola University
  More Information

No publications provided

Responsible Party: Patrick Stiff, Professor of Medicine, Director, Cardinal Bernardin Cancer Center, Loyola University
ClinicalTrials.gov Identifier: NCT00703105     History of Changes
Other Study ID Numbers: 200541
Study First Received: June 19, 2008
Last Updated: June 5, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Loyola University:
ovarian cancer
Tregs
vaccine
Recurrent Ovarian Cancer

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Denileukin diftitox
Interleukin-2
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 30, 2014