Progressive, recurrent or primarily metastatic high-risk malignities
Conditions
Interventions
Product Name: Autologous dendritic cell vaccine producing interleukin 12
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Autologous dendritic cells
Other descriptive name: AUTOLOGO
Sponsors
Masarykova univerzita
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age 1 - 25 years 2. Patient and/or his legal representatives has to sign the informed consent form 3. Histologically confirmed diagnosis of refractory or relapsing or primarily metastatic solid high-risk tumor of child type, treated according to standard methods. (The disease is defined as refractory in the case when the radiology response to 1st line treatment is steady disease, mixed response or progression. High risk is defined as a disease with anticipated 5-year survival less than 25% according to known and used standard methods of treatment.) 4. Performance status – defined according to Karnofsky or Lansky = 50, which equals ECOG categories 0, 1 and 2. Karnofsky score will be used for patients > 10 years, Lansky score will be used for patients = 10 years. 5. Anticipated survival = 10 weeks. 6. Prior therapy: a. Patient must not currently have grade 3 and 4 (evaluated according podle CTCAE v4.0) of toxicity from the prior therapy, i. e. chemotherapy, surgery or radiotherapy or other protocol following treatment. b. Myelosuppressive therapy was finished at least 3 weeks before the planned sampling of tumor tissue. c. Biological treatment: Patient has to discotinue any biological (targeted) treatment at least 7 days before the planned sampling of the tumor tissue in the case of tyrosine kinase inhibitors or at least 3-fold of half life of the administered drug with the upper limit of 6 weeks. d. Immunosuppressive therapy: Patient has to discontinue the immunosuppressive drugs at least 3 weeks prior to tumor tissue sampling. e. Growth factors: should be discontinued at least 7 days prior to planned tumor tissue sampling. f. Patient should be able to undergo surgical procedure aimed at histological verification of refractory, relapsing or metastatic malignity with the objecitve of tumor tissue sampling for manufacture of the autologous dendritic cells vaccine. g. Radiotherapy should be discontinued at least 3 weeks prior to tumor tissue sampling. h. Transplantation: at least 3 months (12 weeks) from autologous transplantation or 6 months (26 weeks) from allogeneic transplantation. 7. Organ functions: a. Adequate bone marrow function defined as: absolute number of neutrofiles = 0,75 thous./µl, thrombocytes = 75 thous./µl (without support by transfusion), hemoglobin = 80 g/l (without support by transfusion) or in patients with infiltration of bone marrow by their fundamental disease it may be defined as: absolute number of neutrophiles = 0,5 thous./µl, thrombocytes = 40 thous./µl (without support by transfusion), hemoglobin = 80 g/l (without support by transfusion). b. Adequate kidney function defined as creatinine clearance GFR = 70 mL/min/1.73 m2, serum creatinine up to maximally 1,5-fold of upper limit for the given age. c. Adequate liver function defined as bilirubin up to maximally 1,5-fold of upper limit for the given age, ALT a AST to maximally 2,5-fold of upper limit for the given age in patient without liver metastases, and up to maximally 5-fold of upper limit for the given age in patients liver metastases. d. Adequate heart function defined as fraction shortening = 27% and ejection fraction = 50% measured by echocardiography. 8. Female patients in fertile age must have negative results of pregnancy test. Are the trial subjects under 18? yes Number of subjects for this age range: 30 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects
Exclusion criteria
Exclusion criteria: 1. Patiensts with autoimmune disease that is not adequately treated 2. Patients who have been treated by autologous dendritic cells vaccine within their prior treatment 3. Patients with uncontrolled hypertension defined as follows: a. Patients aged = 17 years – systolic and diastolic pressure is higher than 95 percentile for their height and age b. Patients aged more than 17 years – systolic and diastolic pressure is = 160/90 mmHg or just diastolic pressure = 90 mmHg 4. Pregnancy, lactation. 5. Patients with uncontrolled psychiatric diagnosis. 6. Pacients with seropositivity: HIV1,2, Treponema pallidum, hepatitis B or hepatitis C. 7. Patients with known hypersensitivity to investigational medicinal product. 8. Patients who were involved in some other clinical trial on medicinal product within 30 days prior to screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Assessment of safety of the autologous vaccine from dendritic cells producing interleukin-12 administered in combination therapy to patients with progressing, relapsing or primarily metastasing high-risk malignities by the analysis of frequency of occurrence of AESI (adverse events of special interest) which are the primary combined safety endpoint.;Secondary Objective: Secondary objectivess - efficacy: a) time to progression b) overall survival c) assessment of objective response to treatment (RECIST) d) CBR (clinical benefit rate) assessment Secondary objectives - safety: Descriptive assessment of the frequency of occurrence, seriousness and types of all found AE.;Primary end point(s): Combined primary endpoint of safety: - frequency of the ocurrence of events defined by the clinical trial protocol as AESI (adverse event of special interest) ;Timepoint(s) of evaluation of this end point: AESI will be analyzed and evaluated after second administration of the IMP to every fifth patient (5+5+5+5+5 process) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy will be evaluated only exploratory as part of the secondary outcomes of the trial. Secondary endpoints - efficacy: a) time to progression b) overall survival c) assessment of objective response to treatment (RECIST) d) CBR (clinical benefit rate) assessment Secondary endpoint of safety: - frequency of the ocurrence of all adverse events assessed in relation to type, seriousness and causality;Timepoint(s) of evaluation of this end point: c) assessment of objective response to treatment (RECIST) - in 12th and 24th month d) CBR (clinical benefit rate) assessment - in 6th and 12th month. Others will be assessed throughout the whole duration of the trial. | — |
Countries
Czech Republic
Contacts
Public ContactCentrum pro klinická hodnocení
Masarykova univerzita - Lékarská fakulta
Outcome results
None listed