Controlled and Selective Depletion of Regulatory T-cell for Cancer Treatment, Efficacy and Safety Study
The primary goal of the proposed clinical trial is to eliminate cancer tumor using an
autologous cell therapy aiming at mounting an efficient immune anti-tumor response by
selectively depleting regulatory T-cell during a controlled amount of time. This strategy
will be tested in patients with hepatic metastases from colorectal who are not eligible for
This is an open-label single cohort phase I-II therapeutic trial. Patients with hepatic
metastases from primary colorectal cancer, not eligible to surgery and relapsing from
conventional chemotherapy and/or targeted therapy, will be included.
Following patient inclusion:
1. A lymphapheresis will be performed at D-15 which will be subjected to cell sorting
/purification of regulatory T cells on the one hand and T lymphocytes depleted from
regulatory T cells (effectors T-cells) on the other, and subsequently frozen and stored
(The procedures for ex vivo regulatory T cell depletion has been validated in a
previous study - AFSSAPS- TC 192) ;
2. A lymphoid-ablative chemotherapy (cyclophosphamide + fludarabine) will be perform from
D1 to D5,
3. Autologous effector T-cells administration will be performed at D7. Efficacy will be
assessed through tumor size change. Change in tumor size will be assessed with CTscans
(RECIST criteria), MRIs (functional criteria following injection: DCEMRI and diffusion
MRI to assess change in cellularity and tumor necrosis and morphological criteria
RECIST), and sonography with contrast injection (to assess vascular microcirculation).
Assessments will be done prior to lymphoid-ablation and then monthly for 9 months.
Safety will be systematically assessed daily during in-patient period using the World
Health Organisation - Common Toxicity Criteria (WHO-CTC).
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Tumor size of hepatic and/or lung metastases, as measured with tomodensitometry (RECIST 1.1 criteria)
from Month 1 to Month 9
David Klatzmann, MD, PhD
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)