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Tha aim of this clinical trial is to evaluate safety and tolerability of autologous peripheral blood differentiated and matured adult dendritic cells. Immunogenicity of the prduct(DC-DELAY) will be evaluated also.
First in human, pilot, open-label, prospective, single-site, non-randomised study
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Single Arm | Experimental | Patients with Lynch Syndrome which will recieve their own dendritic cells to evaluate safety and tolerability |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Autologous Tolerogenic Dendritic cells | Biological | Autologous peripheral blood differentiated and matured adult dendritic cells loaded with Frameshift-derived neopeptides (FSDN) (DC-DELAY). Eligible participants will receive six intradermal immunizations of DC-DELAY at week 0, 2, 4, 6, 8 and 10. |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of participants with grade 3-4 related adverse events for 12 months following the first immunization. | To evaluate the safety and tolerability of autologous peripheral blood differentiated and matured adult dendritic cells loaded with frameshift derived neopeptides (DC-DELAY) in LS carriers. | the first 12 month after the last inmunization |
| Proportion of participants with specific frameshift-derived neoantigens immune response induced by DC-DELAY as measured in peripheral blood by enzyme-linked immune absorbent spot(ELISpot) assay at week 12. | To evaluate specific frameshift-derived neoantigens immunogenicity of DC-DELAY in LS carriers at week 12. NOTE: Immune response will be defined as T-cell reactivity to at least 1 out of 4 of the pools. | At week 12. |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of participants with early immune response induced by DC-DELAY as measured inperipheral blood by ELISpot assay at week 6. | To evaluate the early-term specific frameshift-derived neoantigens immunogenicity of DC-DELAY in LS carriers at week 6. | Week 6 |
| Proportion of participants with long term immune response induced by DC-DELAY as measured in peripheral blood by ELISpot assay at months 6, 12 and 24. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Laura Burunat, Graduate | Contact | 0034 932275400 | 4198 | burunat@recerca.clinic.cat |
| Thomas Walle, Doctor of Medicine | Contact | 0034932275400 | WALLE@recerca.clinic.cat |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Laura Burunat | Recruiting | Barcelona | Barcelona | 08036 | Spain |
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To evaluate the long-term specific frameshift-derived neoantigens immunogenicity of DC-DELAY in LS carriers at 6, 12 and 24 months. |
| Month 6, 12 and 24. |
| Proportion of participants with immune response induced by DC-DELAY as measured in the normal colonic mucosa at month 12. | To evaluate the specific frameshift-derived neoantigens immunogenicity of DC-DELAY in the normal colonic mucosa in LS carriers at month 12. | Month 12 |
| Proportion of participants with mismatch repair deficient colorectal adenomas, advanced neoplasia and/or carcinoma throughout the study duration. | To evaluate the effect of DC-DELAY in LS carriers at week 12 on the burden of mismatch repair deficient colorectal neoplasia throughout the study duration. | Month 12 and month 36 |
| Proportion of participants with LS-related carcinomas throughout the study duration (36 months). | To evaluate the effect of DC-DELAY immunization in LS carriers at week 12 on the burden of LSrelated carcinomas throughout the study duration. | Week 12 and month 36 |
| Number and proportion of participants with related adverse events at 7 days after each DC-DELAY immunization. | To evaluate the safety and tolerability of DC-DELAY | 7 days after each iminization, week 0, week 2, week 4, week 6, uweek 8 and week 10. |
| Number and proportion of participants with grade 3-4 related adverse events throughout the study duration (36 months). | To evaluate the safety and tolerability of DC-DELAY throughout the study duration. | Through study completion, an average of 3 years. |
| ID | Term |
|---|---|
| D003123 | Colorectal Neoplasms, Hereditary Nonpolyposis |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D009386 | Neoplastic Syndromes, Hereditary |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D049914 | DNA Repair-Deficiency Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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