To assess whether procedures and techniques used to derive AKT-DC out of lymph node material influences the quality and number of the AKT-DC end-product.
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. To assess the feasibility of transposing Bioaccell AKT-DC manufacturing
protocol as used by Kimura et al. to the Erasmus MC (EMC).
2. To optimize the generation of AKT-DCs from cytological specimens (EBUS-FNAs
of hilar and mediastinal lymph nodes).
3. Validate production in a relevant study population.
4. Provide necessary documentation to submit a phase 1 clinical trial for
approval [investigational medicinal product dossier (IMPD), investigator
brochure, etc] in the most relevant and feasible clinical setting.
5. To gain a deeper understanding of the mode of action and therapeutic
potential of AKT-DCs by performing a comprehensive analysis of cellular subsets
and immunoreactivity within tumor-draining lymph nodes of NSCLC patients.
Secondary outcome
NA
Background summary
The introduction of the immune checkpoint inhibitors anti-programmed cell death
1 (PD-1)/programmed cell death ligand 1 (PD-L1) revolutionized the treatment of
non-small cell lung cancer (NSCLC), yet some patients are refractory to
treatment and new immunotherapies are under investigation. Autologous expanded
cells from tumour draining lymph nodes (TDLNs), the activated killer T cells
and dendritic cells (AKT-DC), together with adjuvant chemotherapy have been
shown to increase survival of resected primary lung cancer patients. To
generate the AKT-DC, lymph nodes can be obtained during surgery for resectable
stage I-III patient, yet surgery is not indicated for stage IV patients. For
these patients, cytological specimens (endobronchial ultrasound (EBUS)-fine
needle aspirates (FNAs) of hilar and mediastinal lymph nodes) can be used to
obtain lymph node material.
Study objective
To assess whether procedures and techniques used to derive AKT-DC out of lymph
node material influences the quality and number of the AKT-DC end-product.
Study design
Preclinical study to assess the feasibility to culture a lymph node derived
therapeutic cell product.
Study burden and risks
For unresectable NSCLC patients this study design requires additional EBUS
passes from suspicious lymph nodes as well as EBUS from non-suspicious lymph
nodes and non-tumor draining lymph nodes which need to be specifically
collected for this research proposal. For both resectable and stage IV NSCLC,
the cultures will also require an additional peripheral blood draw. This
consists in 1-2 × 109 peripheral blood lymphocytes (PBL) obtained by lymphocyte
apheresis.
This preclinical study serves to prepare a subsequent clinical trial. None of
the cultured cells will therefore be administered to the patients.
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Listed location countries
Age
Inclusion criteria
• Age >=18 years.
• Able to understand the written information and able to give informed consent
according to International Conference of Harmonisation (ICH)/ Good Clinical
Practice (GCP).
• Histologically or radiologically-proven diagnosis of NSCLC.
Exclusion criteria
- Unable to receive extra-additional passes during EBUS and/or to undergo
lymphocyte apheresis.
- Pregnant or lactating
- Subject with any known active serious infection, including human
immunodeficiency
virus (HIV), hepatitis B or C virus, or syphilis infection.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL79806.078.22 |