T Regulatory Lymphocytes (Treg) Depletion for Cancer Treatment Efficacy and Safety Study (STARTREK)
T regulatory lymphocytes were shown to be partly responsible for immune tolerance to cancer cells. In that respect these cells oppose to the mounting of an efficacious immune response needed to cure cancer. To treat advanced metastatic colorectal cancer, the investigators propose an immunotherapy consisting in autologous lymphocytes infusion depleted from T-regulatory cells, associated with a 5-day prior lymphoid-ablative chemotherapy associating cyclophosphamide (day 1 & 2) with fludarabine (day 1 to 5). To administer treatment and monitor chemotherapy safety, patients will be hospitalized for 3 weeks until complete recovery from chemotherapy. Patients will then be followed-up ambulatory for 9 months during which time they will be assessed for tumor size with computed tomography (CT) - scan (primary criteria).
Biological: Adaptive autologous cell immunotherapy
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Controlled and Selective Depletion of Regulatory T-cell for Cancer Treatment, Efficacy and Safety Study|
- Tumor size of hepatic and/or lung metastases, as measured with tomodensitometry (RECIST 1.1 criteria) [ Time Frame: from Month 1 to Month 9 ] [ Designated as safety issue: No ]
- MRI : Assessment of tumor necrosis, cellularity and morphological criteria RECIST 1.1 (functional criteria following injection : DCEMRI and diffusion MRI) [ Time Frame: Month 1 to Month 9 ] [ Designated as safety issue: No ]
- Sonography : assessment of vascular micro-circulation with contrast injection, [ Time Frame: Month 1 to Month 9 ] [ Designated as safety issue: No ]
- Immune cell reconstitution will be assessed through measuring rate of regulatory T-cell reconstitution, [ Time Frame: day 7 to 28 ] [ Designated as safety issue: Yes ]
- Clinical Exam (WHO-CTC), Vital Signs, Adverse events [ Time Frame: day 1 to 28 ] [ Designated as safety issue: Yes ]
- Laboratory test: hepatic function, immune function, haematology [ Time Frame: day 1 to 28 ] [ Designated as safety issue: Yes ]
|Study Start Date:||October 2012|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
|Experimental: adaptive cell immunotherapy||
Biological: Adaptive autologous cell immunotherapy
each patient will undergo a blood cytapheresis to collect circulating lymphocytes. Ex-vivo cell sorting procedure will deplete patient's collected lymphocytes from regulatory T cells. Autologous Treg-depleted lymphocytes will be administered to the patient following a 5-day reduced intensity chemo-therapeutic conditioning.
Other Name: Adaptive autologous cell immunotherapy
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 surgery.
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:
- 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) ;
- A lymphoid-ablative chemotherapy (cyclophosphamide + fludarabine) will be perform from D1 to D5,
- 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).
|Contact: Claude L Bernard, PharmD||+33 (0)email@example.com|
|Service hépato-gastro-enterologie, Pitié-Salpêtrière Hospital||Recruiting|
|Paris, France, 75013|
|Contact: Claude L Bernard, PharmD +33 (0)142176449 firstname.lastname@example.org|
|Principal Investigator: David Klarzmann, MD, PhD|
|Principal Investigator:||David Klatzmann, MD, PhD||Pitié-Salpêtrière Hospital|