IKKb-matured, RNA-loaded Dendritic Cells for Metastasised Uveal Melanoma

Melanoma, Uveal Metastatic Clinical Trial

Official title:

Phase I Vaccination Trial in Metastatic Uveal Melanoma Using IKKb-matured Dendritic Cells Loaded With Autologous Tumor-RNA + RNA Coding for Defined Antigens and Driver Mutations

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04335890
• Other study ID #: DERMA-ER-DC 09
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: June 24, 2020
• Est. completion date: January 30, 2024

Study information

• Verified date: March 2022
• Source: Hasumi International Research Foundation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A Phase I vaccination trial in patients suffering from recently diagnosed metastatic uveal melanoma not cureable with local therapy and needing systemic therapy. IKKb-matured Dendritic Cells loaded with autologous tumor-RNA + RNA coding for defined antigens and driver mutations will be added to a standard therapy chosen by the tumor board (either checkpoint blockade or chemotherapy).

Description:

Intravenous infusion of 7.5 to 30 mio DCIKKb at 9 vaccination time points (week 1, 3, 7, 13, 19, 25, 31, 37 and 42) and in intervals of 2, 4, and 6 intervals of 6 weeks) is scheduled; the first 4 patients will receive reduced doses for the first 4 vaccinations, namely 7.5 mio (1st and 2nd vaccination) and 15 mio (3rd and 4th vaccination) DC followed by the full dose of 30 mio for subsequent vaccinations. Patients number 5 to 8 will receive initially reduced doses of 15 mio (1st and 2nd vaccination) DC for the first 2 vaccinations, and the full dose of 30 mio for subsequent vaccinations. Patients number 8 to 12 will receive the full dose of 30 mio cells from vaccination 1 onwards provided that no major side effects occurred. Patients will be vaccinated in a staggered approach by selectively decelerating release of the vaccine.

DCIKKb = autologous, monocyte-derived DC that are matured with the standard cocktail (TNF-alpha, IL-1 beta, IL-6 and PGE2) and IKKb-RNA loaded by electroporation with 1) autologous PCR-amplified total tumor mRNA, 2) RNA coding for defined tumor associated antigens (TAA) namely gp100, tyrosinase, PRAME, MAGE-A3, IDO) and 3) RNA coding for driver mutations (GNAQ/GNA11Q209 or R183, or the less frequently occurring SF3B1R625, CYSLTR2L129Q or PLCB4D630) by electroporation; RNAs for selected TAAs are in stock and will be transfected into the DCs only if expressed in the individual tumor of a patient (shown by RNA sequencing of the tumor); RNAs for selected driver mutations are in stock and will be loaded into the DCs only if the respective mutation is found (proven by exome and RNA sequencing) in the individual tumor.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 12
• Est. completion date: January 30, 2024
• Est. primary completion date: January 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Histologically confirmed unresectable stage IV metastatic uveal melanoma as per AJCC staging system 2014, 7th edition (updated 2018) not curable with local therapy modalities

• WHO performance status of 0, 1 or 2

• age from 18 and = 75 years

• negative pregnancy test

• signed informed consent

Exclusion Criteria:

• Major serious illness

• evidence for HIV-1, HIV-2, HTLV-1, HBV or HCV infection

• active autoimmune disease requiring immunosuppressive therapy

• splenectomy or radiation therapy of the spleen

• organ allografts

• pregnancy

• lactation

• psychiatric disorders

• severe organic brain syndrome

Related Conditions & MeSH terms

• Melanoma
• Melanoma, Uveal Metastatic

Intervention

Biological:
• Vaccination with IKKb matured Dendritic Cells
IKKb matured autologous monocyte derived dendritic cells loaded with RNAs; intravenous Infusion with a dose escalation starting with 7.5 mio Dendritic Cells for the first vaccination up to 30 mio cells per vaccination

Locations

Country	Name	City	State
Germany	University Hospital Erlangen Dept. of Dermatology	Erlangen	Bavaria

Sponsors (1)

Lead Sponsor	Collaborator
Hasumi International Research Foundation

Country where clinical trial is conducted

Germany, 

References & Publications (3)

Gerer KF, Erdmann M, Hadrup SR, Lyngaa R, Martin LM, Voll RE, Schuler-Thurner B, Schuler G, Schaft N, Hoyer S, Dörrie J. Preclinical evaluation of NF-?B-triggered dendritic cells expressing the viral oncogenic driver of Merkel cell carcinoma for therapeut — View Citation

Pfeiffer IA, Hoyer S, Gerer KF, Voll RE, Knippertz I, Gückel E, Schuler G, Schaft N, Dörrie J. Triggering of NF-?B in cytokine-matured human DCs generates superior DCs for T-cell priming in cancer immunotherapy. Eur J Immunol. 2014 Nov;44(11):3413-28. doi — View Citation

Schuler-Thurner B, Bartz-Schmidt KU, Bornfeld N, Cursiefen C, Fuisting B, Grisanti S, Heindl LM, Holbach L, Keserü M, Knorr H, Koch K, Kruse F, Meiller R, Metz C, Meyer-ter-Vehn T, Much M, Reinsberg M, Schliep S, Seitz B, Schuler G, Süsskind D, Viestenz A — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of DCIKKb	Assesment of side effects using the Common Toxicity Criteria (CTC v4.0)	1 year
Primary	Tolerability of DCIKKb	Assesment of Quality of life using Quality of life EORTC QLQ-C30, Version 2	1 year
Primary	Dose-limiting toxicities (DLTs) of DCIKKb	Assesment of side effects using the Common Toxicity Criteria (CTC v4.0)	1 year
Primary	Maximum tolerated dose (MTD) of DCIKKb	Assesment of side effects using the Common Toxicity Criteria (CTC v4.0)	1 year
Secondary	Prolongation of median overall survival	Assesment of survival	2 years
Secondary	Prolongation of overall survival (OS) after 1 and 2 years	Assesment of survival	2 years
Secondary	Induction of antigen specific CD8+ T cells and / or CD4+ T cells against TAA and mutated drivers	Assesment of immune responses	2 years