Childhood Solid TumorPhase 1NCT02533895
Cancer Immune Therapy for the Treatment of Refractory Solid Tumours of Childhood
A Phase 1 study testing AV0113 DC-CIT and Data evaluation in people with Childhood Solid Tumor, run by Activartis Biotech at 2 sites in Austria.
Trial summary
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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Childhood Solid Tumor
- What is being tested?
- AV0113 DC-CIT and Data evaluation
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 67 participants
- Where
- 2 sitesAustria
- Study dates
- Feb 2000to Oct 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Show all 11Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
Austria2 sites
Department of Orthopaedics, Medical University Vienna
Vienna, 1090
St. Anna Children's Hospital
Vienna, 1090
About this study
Official title: 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.
Read the 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.
- Conditions
- Childhood Solid Tumor
- Being tested
- AV0113 DC-CIT, Data evaluation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AV0113 DC-CITBiological
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.
Data evaluationOther
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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: AV0113 DC-CIT; Other: Data evaluation |
| 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. Receives: Other: Data evaluation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
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.
Measured: 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.
Measured: 10 years
Secondary outcomes (4)
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.
Measured: 4 years
Number of serious adverse events in total and number of serious adverse events related to AV0113 vaccination.
Assessment of the qualitative and quantitative toxicity of DC based anti-tumour immune therapy.
Measured: 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.
Measured: 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.
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2015 (estimated)
- Study startFeb 2000
- Primary completionAug 2015
- Study completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (35)Papers the sponsor has linked to this study.
- Other trials for Childhood Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- Activartis Biotech
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Reinhard Windhager, Dr., Study director, Department of Orthopaedics, Medical University Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02533895
- Sponsor's protocol ID
- TUVAC1
- Status last verified
- Dec 2015
- First submitted
- 23 Jul 2015
- Last updated
- 29 Dec 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 2121321Cheung NK. Immunotherapy. Neuroblastoma as a model. Pediatr Clin North Am. 1991 Apr;38(2):425-41. doi: 10.1016/s0031-3955(16)38085-3.
PubMed 2006085Mayer P, Handgretinger R, Bruchelt G, Schaber B, Rassner G, Fierlbeck G. Activation of cellular cytotoxicity and complement-mediated lysis of melanoma and neuroblastoma cells in vitro by murine antiganglioside antibodies MB 3.6 and 14.G2a. Melanoma Res. 1994 Apr;4(2):101-6. doi: 10.1097/00008390-199404000-00004.
PubMed 8069095Cheung NK, Lazarus H, Miraldi FD, Abramowsky CR, Kallick S, Saarinen UM, Spitzer T, Strandjord SE, Coccia PF, Berger NA. Ganglioside GD2 specific monoclonal antibody 3F8: a phase I study in patients with neuroblastoma and malignant melanoma. J Clin Oncol. 1987 Sep;5(9):1430-40. doi: 10.1200/JCO.1987.5.9.1430.
PubMed 3625258Handgretinger R, Baader P, Dopfer R, Klingebiel T, Reuland P, Treuner J, Reisfeld RA, Niethammer D. A phase I study of neuroblastoma with the anti-ganglioside GD2 antibody 14.G2a. Cancer Immunol Immunother. 1992;35(3):199-204. doi: 10.1007/BF01756188.
PubMed 1638557Murray JL, Cunningham JE, Brewer H, Mujoo K, Zukiwski AA, Podoloff DA, Kasi LP, Bhadkamkar V, Fritsche HA, Benjamin RS, et al. Phase I trial of murine monoclonal antibody 14G2a administered by prolonged intravenous infusion in patients with neuroectodermal tumors. J Clin Oncol. 1994 Jan;12(1):184-93. doi: 10.1200/JCO.1994.12.1.184.
PubMed 8270976Khanna C, Anderson PM, Hasz DE, Katsanis E, Neville M, Klausner JS. Interleukin-2 liposome inhalation therapy is safe and effective for dogs with spontaneous pulmonary metastases. Cancer. 1997 Apr 1;79(7):1409-21. doi: 10.1002/(sici)1097-0142(19970401)79:73.0.co;2-3.
PubMed 9083164Sinkovics JG, Horvath JC. Vaccination against human cancers (review). Int J Oncol. 2000 Jan;16(1):81-96. doi: 10.3892/ijo.16.1.81.
PubMed 10601552Pardoll DM. Inducing autoimmune disease to treat cancer. Proc Natl Acad Sci U S A. 1999 May 11;96(10):5340-2. doi: 10.1073/pnas.96.10.5340. No abstract available.
PubMed 10318881Roskrow MA, Dilloo D, Suzuki N, Zhong W, Rooney CM, Brenner MK. Autoimmune disease induced by dendritic cell immunization against leukemia. Leuk Res. 1999 Jun;23(6):549-57. doi: 10.1016/s0145-2126(99)00045-4.
PubMed 10374848Darnell RB, DeAngelis LM. Regression of small-cell lung carcinoma in patients with paraneoplastic neuronal antibodies. Lancet. 1993 Jan 2;341(8836):21-2. doi: 10.1016/0140-6736(93)92485-c.
PubMed 8093269Darnell RB. Onconeural antigens and the paraneoplastic neurologic disorders: at the intersection of cancer, immunity, and the brain. Proc Natl Acad Sci U S A. 1996 May 14;93(10):4529-36. doi: 10.1073/pnas.93.10.4529.
PubMed 8643438Connolly AM, Pestronk A, Mehta S, Pranzatelli MR 3rd, Noetzel MJ. Serum autoantibodies in childhood opsoclonus-myoclonus syndrome: an analysis of antigenic targets in neural tissues. J Pediatr. 1997 Jun;130(6):878-84. doi: 10.1016/s0022-3476(97)70272-5.
PubMed 9202608Aichele P, Kyburz D, Ohashi PS, Odermatt B, Zinkernagel RM, Hengartner H, Pircher H. Peptide-induced T-cell tolerance to prevent autoimmune diabetes in a transgenic mouse model. Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):444-8. doi: 10.1073/pnas.91.2.444.
PubMed 8290546Aichele P, Brduscha-Riem K, Zinkernagel RM, Hengartner H, Pircher H. T cell priming versus T cell tolerance induced by synthetic peptides. J Exp Med. 1995 Jul 1;182(1):261-6. doi: 10.1084/jem.182.1.261.
PubMed 7540654
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Monocyte-derived Dendritic Cells Loaded With Tumour Cell Lysates for the Treatment of Refractory Solid Tumours of Childhood
- ClinicalTrials.gov ID
- NCT02533895
- Acronym / sponsor ID
- TUVAC1
- Conditions
- Childhood Solid Tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- Activartis BiotechIndustry (pharma, biotech, devices)
- Study start
- Feb 2000
- Primary completion
- Aug 2015 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 27 Aug 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment with AV0113 | Experimental | Biological: AV0113 DC-CIT, Other: Data evaluation14 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 | Other: Data evaluationIn 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AV0113 DC-CITMature 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. | Biological | Treatment with AV0113 |
| Data evaluationFor 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, Treatment with AV0113 |
Primary outcome
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.
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.
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.
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.
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.
4 secondary outcomes
Number of treatment patients in which vaccination with AV0113 was feasible.
Time frame: 4 years
Number of serious adverse events in total and number of serious adverse events related to AV0113 vaccination.
Time frame: 4 years
Fraction of patients with immune response to vaccine antigens as measured by DTH testing.
Time frame: 4 years
Listings of in-vitro immunological variables with an association with survival as measured by Cox regression.
Time frame: 4 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2015.
- Background: PubMed 2121321Bleyer 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.
- Background: PubMed 2006085Cheung NK. Immunotherapy. Neuroblastoma as a model. Pediatr Clin North Am. 1991 Apr;38(2):425-41. doi: 10.1016/s0031-3955(16)38085-3.
- Background: PubMed 8069095Mayer P, Handgretinger R, Bruchelt G, Schaber B, Rassner G, Fierlbeck G. Activation of cellular cytotoxicity and complement-mediated lysis of melanoma and neuroblastoma cells in vitro by murine antiganglioside antibodies MB 3.6 and 14.G2a. Melanoma Res. 1994 Apr;4(2):101-6. doi: 10.1097/00008390-199404000-00004.
- Background: PubMed 3625258Cheung NK, Lazarus H, Miraldi FD, Abramowsky CR, Kallick S, Saarinen UM, Spitzer T, Strandjord SE, Coccia PF, Berger NA. Ganglioside GD2 specific monoclonal antibody 3F8: a phase I study in patients with neuroblastoma and malignant melanoma. J Clin Oncol. 1987 Sep;5(9):1430-40. doi: 10.1200/JCO.1987.5.9.1430.
- Background: PubMed 1638557Handgretinger R, Baader P, Dopfer R, Klingebiel T, Reuland P, Treuner J, Reisfeld RA, Niethammer D. A phase I study of neuroblastoma with the anti-ganglioside GD2 antibody 14.G2a. Cancer Immunol Immunother. 1992;35(3):199-204. doi: 10.1007/BF01756188.
- Background: PubMed 8270976Murray JL, Cunningham JE, Brewer H, Mujoo K, Zukiwski AA, Podoloff DA, Kasi LP, Bhadkamkar V, Fritsche HA, Benjamin RS, et al. Phase I trial of murine monoclonal antibody 14G2a administered by prolonged intravenous infusion in patients with neuroectodermal tumors. J Clin Oncol. 1994 Jan;12(1):184-93. doi: 10.1200/JCO.1994.12.1.184.
- Background: PubMed 9083164Khanna C, Anderson PM, Hasz DE, Katsanis E, Neville M, Klausner JS. Interleukin-2 liposome inhalation therapy is safe and effective for dogs with spontaneous pulmonary metastases. Cancer. 1997 Apr 1;79(7):1409-21. doi: 10.1002/(sici)1097-0142(19970401)79:73.0.co;2-3.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Reinhard Windhager, Dr. study director
Department of Orthopaedics, Medical University Vienna
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AV0113 DC-CIT and Data evaluation in people with Childhood Solid Tumor, run by Activartis Biotech at 2 sites in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02533895, which also lists 35 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Dec 2015.