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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

Phase 2
18 Years
Open (Enrolling)
Ovarian Cancer

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Trial Information

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

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

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

- Patients with known brain metastases

Type of Study:


Study Design:

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

Outcome Measure:

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

Outcome Time Frame:

days 45 and 62 post vaccine

Safety Issue:


Principal Investigator

Patrick Stiff, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Loyola University


United States: Food and Drug Administration

Study ID:




Start Date:

October 2008

Completion Date:

July 2013

Related Keywords:

  • Ovarian Cancer
  • ovarian cancer
  • Tregs
  • vaccine
  • Recurrent Ovarian Cancer
  • Ovarian Neoplasms



Loyola Univeristy Medical Center, Cardinal Bernardin Cancer Center Maywood, Illinois  60153