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Controlled and Selective Depletion of Regulatory T-cell for Cancer Treatment, Efficacy and Safety Study

Phase 1/Phase 2
18 Years
65 Years
Open (Enrolling)
Colorectal Cancer

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Trial Information

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).

Inclusion Criteria:

- Colon or rectal adenocarcinoma histologically proven;

- Hepatic or lung metastasis (at least one with size >1cm on CT-scan);

- Not eligible for surgery;

- Prior treatment with fluoropyrimidines, CPT11, oxaliplatine and EGFR antibodies
(Cetuximab ou Panitumumab) ± bevacizumab; When tumor has a mutated Kras, prior
treatment with EGFR antibodies is not mandatory;

- No local recurrence (on CT-scan, sonogram and/or colonoscopy);

- Karnofsky index > 70 and PS 0 or 1;

- ASA Score < 3 ;

- Absence of chronic hepatopathy ;

- Lab test : WBC: neutrophil> 2.0 109 / l, lymphocytes > 1.5 109 / l; creatinine < 1.5
x ULN or clearance ≥ 60 ml/min; AST et ALT< 5 x ULN, alkaline phosphatases < 3 x ULN;
LDH < 3 x ULN; negative Coombs test ;

- Signed informed consent.

Exclusion Criteria:

- Peritoneal carcinosis on CT-scan, MRI or PET-scan;

- Contra-indication to MRI;

- Patient with known allergy to iodinated contrast agent, gadolinium or Sulfate
Hexafluoron ;

- Presence of metastasis at sites other than lung and liver;

- Documented history of auto-immune disease and/ or progressing disease;

- Infection at whatever site;

- Documented history of allo- or autograft;

- Undernutrition, BMI < 18;

- History of other cancer < 5 years (excluding cancer in situ of the cervix and
baso-cellular tumor of the skin) or progressing disease;

- Women of child bearing age without contraception , or pregnant or breast feeding.

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Tumor size of hepatic and/or lung metastases, as measured with tomodensitometry (RECIST 1.1 criteria)

Outcome Time Frame:

from Month 1 to Month 9

Safety Issue:


Principal Investigator

David Klatzmann, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Pitié-Salpêtrière Hospital


France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Study ID:




Start Date:

October 2012

Completion Date:

December 2013

Related Keywords:

  • Colorectal Cancer
  • Advanced Colorectal Cancer
  • Hepatic and/or lung metastasis
  • Adaptive autologous cell immunotherapy
  • T- regulatory lymphocyte depletion
  • Neo-adjuvant reduced intensity chemotherapeutic conditioning
  • Colorectal Neoplasms