Denileukin Diftitox Followed by Vaccine Therapy in Treating Patients With Metastatic Cancer

NCT ID: NCT00128622

Last Updated: 2012-11-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-09-30

Study Completion Date

2009-05-31

Brief Summary

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RATIONALE: Combinations of biological substances in denileukin diftitox may be able to carry cancer-killing substances directly to the cancer cells. Vaccines made from a gene-modified virus and a person's white blood cells may help the body build an effective immune response to kill cancer cells. Giving denileukin diftitox together with vaccine therapy may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects of giving denileukin diftitox together with vaccine therapy in treating patients with metastatic cancer that expresses carcinoembryonic antigen.

Detailed Description

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OBJECTIVES:

Primary

* Determine the safety and feasibility of two different schedules of denileukin diftitox followed by active immunotherapy comprising autologous dendritic cells infected with recombinant fowlpox-CEA(6D)-TRICOM vaccine in patients with metastatic CEA-expressing malignancies.

Secondary

* Determine the immune response to this regimen in these patients.
* Determine, preliminarily, clinical response rate and/or time to progression in patients with assessable disease treated with this regimen.

OUTLINE: Patients undergo leukapheresis for collection of peripheral blood mononuclear cells (PBMCs). PBMCs are cultured with sargramostim (GM-CSF) and interleukin-4 for the production of dendritic cells( DC). DC are mixed with recombinant fowlpox-TRICOM to produce the vaccine. Patients are assigned to 1 of 2 cohorts according to timing of study enrollment.

* Cohort 1: Patients receive denileukin diftitox IV over at least 15 minutes once in week 0 and vaccine therapy comprising autologous DC infected with recombinant fowlpox-CEA (6D)-TRICOM vaccine intradermally and subcutaneously once in weeks 0 (beginning 4 days after the denileukin diftitox infusion), 3, 6, and 9. If \< 2 of 6 patients experience dose-limiting toxicity, a second cohort of patients is enrolled.
* Cohort 2: Patients receive denileukin diftitox as in cohort 1 once in weeks 0, 3, 6, and 9 and vaccine as in cohort 1.

In both cohorts, treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed annually for up to 15 years.

PROJECTED ACCRUAL: A total of 6-12 patients (6 per cohort) will be accrued for this study.

Conditions

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Breast Cancer Colorectal Cancer Lung Cancer Pancreatic Cancer Unspecified Adult Solid Tumor, Protocol Specific

Keywords

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male breast cancer recurrent breast cancer stage IV breast cancer recurrent colon cancer stage IV colon cancer recurrent rectal cancer stage IV rectal cancer recurrent pancreatic cancer extensive stage small cell lung cancer recurrent non-small cell lung cancer recurrent small cell lung cancer stage IV non-small cell lung cancer unspecified adult solid tumor, protocol specific stage IV pancreatic cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Denileukin Diftitox plus vaccine

This is a single arm Phase I safety study.

Group Type EXPERIMENTAL

denileukin diftitox

Intervention Type BIOLOGICAL

recombinant fowlpox-CEA(6D)/TRICOM vaccine

Intervention Type BIOLOGICAL

therapeutic autologous dendritic cells

Intervention Type BIOLOGICAL

Interventions

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denileukin diftitox

Intervention Type BIOLOGICAL

recombinant fowlpox-CEA(6D)/TRICOM vaccine

Intervention Type BIOLOGICAL

therapeutic autologous dendritic cells

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* No other active acute or chronic infection
* No history of allergies to eggs or any component of the study vaccine, denileukin diftitox, or diphtheria toxin NOTE: \*Patients with a positive anti-nuclear antibody (ANA) ≤ 1:256 with no other evidence of autoimmune disease are eligible

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 4 months after completion of study treatment
* No acute or chronic skin disorder that would preclude study treatment
* No other malignancy within the past 5 years except nonmelanoma skin cancer, controlled carcinoma in situ of the cervix, or controlled superficial bladder cancer
* No psychological or medical impediment that would preclude study compliance
* No other serious acute or chronic illness that would preclude study treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

* See Disease Characteristics
* Prior vaccine, dendritic cell, or CEA-targeted immunotherapy allowed
* At least 4 weeks since prior and no other concurrent immunotherapy
* Concurrent palliative single-agent trastuzumab for breast cancer allowed provided patient has been on therapy for ≥ 3 months before study entry

Chemotherapy

* See Disease Characteristics
* At least 4 weeks since prior and no concurrent chemotherapy

Endocrine therapy

* At least 4 weeks since prior hormonal therapy
* At least 6 weeks since prior steroid therapy except steroids used as premedication for chemotherapy or contrast-enhanced studies
* No concurrent steroids, including corticosteroids administered to manage toxic effects from dendritic cell or denileukin diftitox administration
* Concurrent palliative endocrine therapy for breast cancer allowed provided patient has been on therapy for ≥ 3 months before study entry

Radiotherapy

* At least 4 weeks since prior and no concurrent radiotherapy

Surgery

* See Disease Characteristics

Other

* Recovered from all prior therapy
* At least 4 weeks since prior investigational drugs or procedures
* At least 4 weeks since other prior therapy
* No other concurrent immunosuppressive therapy (e.g., azathioprine or cyclosporine)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

H. Kim Lyerly

OTHER

Sponsor Role lead

Responsible Party

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H. Kim Lyerly

Professor, Gen & Thor Surgery

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Michael A. Morse, MD

Role: STUDY_CHAIR

Duke Cancer Institute

Locations

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Lombardi Comprehensive Cancer Center at Georgetown University Medical Center

Washington D.C., District of Columbia, United States

Site Status

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Site Status

Countries

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United States

References

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Schonfeld K, Mahnke K, Schallenberg S, et al.: Treatment of melanoma bearing individuals with ONTAK® depletes regulatory T cells resulting in an augmented immune response following vaccination. [Abstract] J Invest Dermatol 126 (Suppl S3): A-594, s101, 2006.

Reference Type BACKGROUND

Morse MA, Hobeika AC, Osada T, Serra D, Niedzwiecki D, Lyerly HK, Clay TM. Depletion of human regulatory T cells specifically enhances antigen-specific immune responses to cancer vaccines. Blood. 2008 Aug 1;112(3):610-8. doi: 10.1182/blood-2008-01-135319. Epub 2008 Jun 2.

Reference Type DERIVED
PMID: 18519811 (View on PubMed)

Other Identifiers

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DUMC-NCI-7042

Identifier Type: -

Identifier Source: secondary_id

NCI-7042

Identifier Type: -

Identifier Source: secondary_id

CDR0000437795

Identifier Type: -

Identifier Source: org_study_id