Cancer Immune Therapy for the Treatment of Refractory Solid Tumours of Childhood

December 28, 2015 updated by: Activartis Biotech

Monocyte-derived Dendritic Cells Loaded With Tumour Cell Lysates for the Treatment of Refractory Solid Tumours of Childhood

This is an un-blinded Phase 1 study in which 21 patients suffering from solid advanced paediatric malignancies (14 sarcoma and 7 non-sarcoma patients) are treated with AV0113, an anti-tumour immune therapy with autologous Dendritic Cells (DCs) loaded with tumour cell lysates, in order to investigate its safety and feasibility.

For obtaining a clearer picture of AV0113's utility in the treatment of bone and soft tissue sarcoma, a long-term (LT) follow-up investigation of the 14 sarcoma patients, which will be treated using the AV0113 Dendritic Cell Cancer Immune Therapy (DC-CIT) technology is planned, in order to gather first evidence for a potential LT effect of DC-CIT with AV0113.

Furthermore, a comparison of the 14 sarcoma patients treated with AV0113 DC-CIT with a cohort of matched historic control patients that were treated using standard of care will be conducted. It is planned to analyse 42 historic control sarcoma patients that will be matched for disease, recurrences, relapses etc.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

In this phase I trial 21 paediatric patients with solid tumours of childhood (14 sarcoma and 7 non-sarcoma patients) that have exhausted all conventional treatment options are recruited for the treatment with AV0113.

Peripheral blood mononuclear cells (MNCs) will be obtained from patients by leukocyte apheresis. Monocytes enriched by density gradient centrifugation from MNCs will be used to generate immature DCs by cultivation in recombinant human interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating-factor (GM-CSF). These immature DCs will be loaded with autologous tumour cell lysates obtained by needle biopsy or surgery prior to tumour vaccination.The antigen loaded immature DCs will then receive a final maturation stimulus transmitted by exposure to lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). Maturation enables DCs to present antigen with high efficiency to T-lymphocytes. Subsequently, mature loaded DCs will be injected subcutaneously close to tumour free lymph nodes or intra-nodally into tumour free lymph nodes at weekly intervals for at least 6 weeks.

It is anticipated to establish the feasibility and safety of tumour vaccination in the described clinical setting and to find some clinical and/or experimental evidence for the induction of an anti-tumour immune response.

For obtaining a clearer picture of AV0113's utility in the treatment of bone and soft tissue sarcoma, a long-term (LT) follow-up investigation of the 14 Sarcoma patients, which will be treated using the AV0113 DC-CIT technology is planned, in order to gather first evidence for a potential LT effect of DC-CIT with AV0113.

Furthermore, a comparison of the 14 sarcoma patients treated with AV0113 DC-CIT with a cohort of matched historic control patients that were treated using standard of care will be conducted. It is planned to analyse 42 historic control sarcoma patients that will be matched for disease, recurrences, relapses etc.

Study Type

Interventional

Enrollment (Actual)

67

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Vienna, Austria, 1090
        • St. Anna Children's Hospital
      • Vienna, Austria, 1090
        • Department of Orthopaedics, Medical University Vienna

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Inclusion criteria for the safety and feasibility testing of AV0113

  • Male and female patients with a malignant neoplasia shall be eligible for this protocol provided they have no more "conventional" treatment options and have measurable disease. There is no age limit for participation in this study provided that the tumour is typical for the group of refractory solid neoplasias of childhood.
  • Patients must not be HIV-positive.
  • Patients must have primary tumour tissue or cells available at sufficient number to allow treatment according to the protocol.
  • Patients or legal guardians must sign an informed consent indicating that they are aware this is a research study and have been told of its possible benefits and toxic side effects. Patients or their guardians will be given a copy of the consent form.

Inclusion criteria for patients included in the long-term follow up and comparison with historic controls

  • Patients suffering from bone or soft tissue sarcoma that received treatment with AV0113 or are documented in the database of the Medical University Vienna's Department of Orthopaedics.
  • At least one disease recurrence after first CR or worse disease condition (e.g.: never reached CR).
  • Diagnosis between 1992-2003 and/or "inclusion time point" during the years 2000-2004.
  • Availability of date of death or of confirmation that patient is still alive (for the currentness of confirmation that patients are still alive only the time span from 1 April 2014 to 1 April 2015 is accepted).
  • Patients not older than 27 years at their ITP.

Exclusion Criteria:

Exclusion criteria for the safety and feasibility testing of AV0113

  • Any of the inclusion criteria not met.
  • Any condition which, in the investigator's opinion, may pose a risk to the patient or will interfere with the study objectives.

Exclusion criteria for patients included in the long-term follow up and comparison with historic controls

  • Date of "inclusion time point" and death or confirmation that patient is still alive at time of evaluation not available.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment with AV0113

14 sarcoma and 7 non-sarcoma are treated with AV0113, an anti-tumour immune therapy with autologous DCs loaded with tumour cell lysates in order to establish the feasibility and safety of tumour vaccination.

Peripheral blood mononuclear cells (MNCs) are obtained from patients by leukocyte apheresis. Monocytes enriched by density gradient centrifugation from MNCs will be used to generate immature DCs. These immature DCs will be loaded with autologous tumour cell lysates obtained by needle biopsy or surgery prior to tumour vaccination. The antigen loaded immature DCs will then receive a final maturation stimulus transmitted by exposure to lipopolysaccharide and interferon-gamma. Maturation enables DCs to present antigen with high efficiency to T-lymphocytes.
Biological: AV0113 DC-CIT
Mature loaded DCs will be injected intra-nodally into tumour free lymph nodes or subcutaneously close to tumour free lymph nodes at weekly intervals for at least 6 weeks.
Other: Data evaluation

For obtaining a clearer picture of AV0113's utility in the treatment of bone and soft tissue sarcoma, a LT follow-up investigation of the 14 Sarcoma patients, which will be treated using the AV0113 DC-CIT technology, is planned, in order to gather first evidence for a potential LT effect of DC-CIT with AV0113.

Furthermore, a comparison of the 14 sarcoma patients treated with AV0113 DC-CIT with a cohort of matched historic control patients that were treated using standard of care will be conducted. It is planned to analyse 42 control sarcoma patients that will be matched for disease, recurrences, relapses etc
Other: Historic control
In order to be able to compare the survival data of 14 sarcoma patients treated with AV0113, 42 historic control sarcoma patients from the data base of the Department of Orthopaedics, Medical University Vienna, that will be matched for disease, recurrences, relapses etc. will be included into this study.
Other: Data evaluation

For obtaining a clearer picture of AV0113's utility in the treatment of bone and soft tissue sarcoma, a LT follow-up investigation of the 14 Sarcoma patients, which will be treated using the AV0113 DC-CIT technology, is planned, in order to gather first evidence for a potential LT effect of DC-CIT with AV0113.

Furthermore, a comparison of the 14 sarcoma patients treated with AV0113 DC-CIT with a cohort of matched historic control patients that were treated using standard of care will be conducted. It is planned to analyse 42 control sarcoma patients that will be matched for disease, recurrences, relapses etc

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determination of the long-term effect of AV0113 by counting the total survival time in days measured from inclusion time point to death.
Time Frame: 15 years

Total survival time of sarcoma patients, that underwent DC-CIT, measured from the "inclusion time point" (ITP) until death, independent of subsequent surgeries after DC-CIT.

In the treatment group the inclusion time point (ITP) is defined as the day of surgery of the surgically treated relapse immediately before DC-CIT.
15 years
Comparison of total survival times in days of sarcoma patients treated with AV0113 with total survival times of a cohort of matched historic control patients.
Time Frame: 15 Years

Total survival time of sarcoma patients, that underwent DC-CIT, measured from the "inclusion time point" (ITP) until death, independent of subsequent surgeries after DC-CIT; in comparison with the survival time of matched historical control patients measured from the ITP until death independent of subsequent surgeries.

In the treatment group the ITP is defined as the day of surgery of the surgically treated relapse immediately before DC-CIT. In the control group the ITP is defined as the time of the surgery performed for the treatment of the xth relapse after which the matching patient of the treatment group received DC-CIT.
15 Years
Comparison of the percentage of treatment patients still alive after 2 years with the percentage of matched historic control patients still alive after 2 years.
Time Frame: 2 years

Percentage of sarcoma patients that underwent DC-CIT with AV0113, still alive after 2 years measured from the ITP independent of subsequent surgeries after DC-CIT; in comparison with the percentage of matched historical control patients still alive after 2 years measured from the ITP, independent of subsequent surgeries.

In the treatment group the ITP is defined as the day of surgery of the surgically treated relapse immediately before DC-CIT. In the control group the ITP is defined as the time of the surgery performed for the treatment of the xth relapse after which the matching patient of the treatment group received DC-CIT.
2 years
Comparison of the percentage of treatment patients still alive after 5 years with the percentage of matched historic control patients still alive after 5 years.
Time Frame: 5 years

Percentage of sarcoma patients that underwent DC-CIT with AV0113, still alive after 5 years measured from the ITP independent of subsequent surgeries after DC-CIT; in comparison with the percentage of matched historical control patients still alive after 5 years measured from the ITP, independent of subsequent surgeries.

In the treatment group the ITP is defined as the day of surgery of the surgically treated relapse immediately before DC-CIT. In the control group the ITP is defined as the time of the surgery performed for the treatment of the xth relapse after which the matching patient of the treatment group received DC-CIT.
5 years
Comparison of the percentage of treatment patients still alive after 10 years with the percentage of matched historic control patients still alive after 10 years.
Time Frame: 10 years

Percentage of sarcoma patients that underwent DC-CIT with AV0113, still alive after 10 years measured from the ITP independent of subsequent surgeries after DC-CIT; in comparison with the percentage of matched historical control patients still alive after 10 years measured from the ITP, independent of subsequent surgeries.

In the treatment group the ITP is defined as the day of surgery of the surgically treated relapse immediately before DC-CIT. In the control group the ITP is defined as the time of the surgery performed for the treatment of the xth relapse after which the matching patient of the treatment group received DC-CIT.
10 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of treatment patients in which vaccination with AV0113 was feasible.
Time Frame: 4 years
Establishment of the feasibility of anti-tumour immune therapy with autologous DCs loaded with tumour cell lysates for the treatment of patients suffering from solid advanced paediatric malignancies.
4 years
Number of serious adverse events in total and number of serious adverse events related to AV0113 vaccination.
Time Frame: 4 years
Assessment of the qualitative and quantitative toxicity of DC based anti-tumour immune therapy.
4 years
Fraction of patients with immune response to vaccine antigens as measured by DTH testing.
Time Frame: 4 years
In vivo evaluation of the vaccination efficiency by delayed-type hypersensitivity (DTH) testing.
4 years
Listings of in-vitro immunological variables with an association with survival as measured by Cox regression.
Time Frame: 4 years
In vitro characterization of the anti-tumour immunity generated by the tumour vaccination.
4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Activartis Biotech

Investigators

  • Study Director: Reinhard Windhager, Dr., Department of Orthopaedics, Medical University Vienna

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2000

Primary Completion (Actual)

August 1, 2015

Study Completion (Actual)

October 1, 2015

Study Registration Dates

First Submitted

July 23, 2015

First Submitted That Met QC Criteria

August 26, 2015

First Posted (Estimate)

August 27, 2015

Study Record Updates

Last Update Posted (Estimate)

December 29, 2015

Last Update Submitted That Met QC Criteria

December 28, 2015

Last Verified

December 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TUVAC1

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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