Vaccination of Metastatic Breast Cancer Patients With a CD80-modified Allogeneic Cancer Cell Line (KS2422) (KS2422-vacc)

Phase 1 Study: Induction of Systemic Immune Responses in Metastatic Breast Cancer Patients by Vaccination With a CD80-modified, Devitalized HLA-*A0201+ Breast Cancer Cell Line (KS24.22)

In the last few years there has been a great attempt to develop active immunotherapies for breast cancer patients (BCPs) using undefined as well as selected antigens to activate tumor specific T-lymphocytes. The purpose of this phase-I study was to determine the safety and feasibility of vaccinations with an allogeneic breast cancer cell line, KS24.22, genetically modified to express CD80 and Her-2/neu, and to evaluate the efficacy of inducing tumor antigen-specific immune responses in human leukocyte antigen(HLA)-A*02-matched patients with metastatic breast cancer.

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Biological: KS24.22 cells

Detailed Description

The trial was designed as an open label phase-I. Informed consent was given twice by the patients (1st for HLA-typing, 2nd for participation in the vaccination trial).

The first four vaccinations, which were given every two weeks, were followed by four monthly vaccinations. Additional vaccinations were permitted on request for patients who exhibited stable disease (SD).

Immediately before administration, KS24.22 cells were thawed and lethally irradiated. KS24.22 cells were adjusted to 10E7/ml in Ringer-Lactate-solution, transferred to 1 ml syringes and stored on ice until injected within a time frame of 2h. Vaccinations were given i.d. in the thigh with a total volume of 1 ml divided between two injection sites.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Tuebingen, Germany, 72076
    • Univ. of Tuebingen, Dep. Obst. and Gynecology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• proven diagnosis of carcinoma of the breast with distant metastatic disease
• patient received either anthracycline- or taxane-based chemotherapy ("state of the art")
• Karnofsky Score (performance status) 80%
• HLA-*A0201-positive
• minimum life expectancy of 6 month
• written informed consent
• activation of patient's T-lymphocytes by mitogen antibodies and the cell line used for vaccination

Exclusion Criteria:

• manifestation of CNS metastases
• immunosuppressive disease like AIDS, autoimmune disease
• no serious concomitant systemic medical disorders or active acute or systemic infection
• pregnancy
• chemotherapies or radiotherapies in the 4 weeks preceding study entry
• biological response modifiers (antibodies, TNF, cytokines) or other immune therapies in the 6 weeks preceding study entry (exclusion: hematopoetic growth factors)
• organ transplanted patients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: KS24.22-vaccination; The first four vaccinations, which were given every two weeks, were followed by four monthly vaccinations. Additional vaccinations were permitted on request for patients who exhibited stable disease (SD). Immediately before administration, KS24.22 cells were thawed and lethally irradiated. KS24.22 cells were adjusted to 10E7/ml in Ringer-Lactate-solution, transferred to 1 ml syringes and stored on ice until injected within a time frame of 2h. Vaccinations were given i.d. in the thigh with a total volume of 1 ml divided between two injection sites.

Biological: KS24.22 cells; The first four vaccinations, which were given every two weeks, were followed by four monthly vaccinations. Additional vaccinations were permitted on request for patients who exhibited stable disease (SD). Immediately before administration, KS24.22 cells were thawed and lethally irradiated (200 gray). KS24.22 cells were adjusted to 107/ml in Ringer-Lactate-solution, transferred to 1 ml syringes and stored on ice until injected within a time frame of 2h. Vaccinations were given i.d. in the thigh with a total volume of 1 ml divided between two injection sites.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
feasibility
safety of KS24.22 administration	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
overall survival
progression free survival
immunological response	2 years

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen
• Collaborators: Paul Ehrlich Institute, Langen, Germany
• Investigators: Principal Investigator: Diethelm Wallwiener, University Hospital Tuebingen

Publications and helpful links

General Publications

• Guckel B, Stumm S, Rentzsch C, Marme A, Mannhardt G, Wallwiener D. A CD80-transfected human breast cancer cell variant induces HER-2/neu-specific T cells in HLA-A*02-matched situations in vitro as well as in vivo. Cancer Immunol Immunother. 2005 Feb;54(2):129-40. doi: 10.1007/s00262-004-0583-z. Epub 2004 Sep 9.

Study record dates

Study Major Dates

• Study Start: March 1, 2002
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: May 18, 2010
• First Submitted That Met QC Criteria: May 19, 2010
• First Posted (Estimate): May 20, 2010

Study Record Updates

• Last Update Posted (Estimate): May 20, 2010
• Last Update Submitted That Met QC Criteria: May 19, 2010
• Last Verified: May 1, 2010

More Information

Terms related to this study

• Keywords: immunotherapy; vaccination; metastatic breast cancer; breast cancer stage IV; CD80
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 01 KV 9540