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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment with AV0113 | Experimental | 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. |
|
| Historic control | Other | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AV0113 DC-CIT | Biological | 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. |
| 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. | 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. | 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. | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of treatment patients in which vaccination with AV0113 was feasible. | 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. |
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Inclusion Criteria:
Inclusion criteria for the safety and feasibility testing of AV0113
Inclusion criteria for patients included in the long-term follow up and comparison with historic controls
Exclusion Criteria:
Exclusion criteria for the safety and feasibility testing of AV0113
Exclusion criteria for patients included in the long-term follow up and comparison with historic controls
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| Name | Affiliation | Role |
|---|---|---|
| Reinhard Windhager, Dr. | Department of Orthopaedics, Medical University Vienna | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Orthopaedics, Medical University Vienna | Vienna | 1090 | Austria | |||
| St. Anna Children's Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 2121321 | Background | Bleyer WA. The impact of childhood cancer on the United States and the world. CA Cancer J Clin. 1990 Nov-Dec;40(6):355-67. doi: 10.3322/canjclin.40.6.355. No abstract available. | |
| 2006085 | Background | Cheung NK. Immunotherapy. Neuroblastoma as a model. Pediatr Clin North Am. 1991 Apr;38(2):425-41. doi: 10.1016/s0031-3955(16)38085-3. |
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Jun 24, 2016 | |
| Reset | Aug 5, 2016 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Jun 24, 2016 | Aug 5, 2016 |
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| Data evaluation | Other | 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 |
|
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. | 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 |
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. | 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. | In vitro characterization of the anti-tumour immunity generated by the tumour vaccination. | 4 years |
| Vienna |
| 1090 |
| Austria |
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