T Regulatory Lymphocytes (Treg) Depletion for Cancer Treatment Efficacy and Safety Study (STARTREK)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00986518
Recruitment Status : Completed
First Posted : September 30, 2009
Last Update Posted : November 25, 2013
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Colorectal Cancer Biological: Adaptive autologous cell immunotherapy Phase 1 Phase 2

Detailed Description:

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:

  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).

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Controlled and Selective Depletion of Regulatory T-cell for Cancer Treatment, Efficacy and Safety Study
Study Start Date : October 2012
Actual Primary Completion Date : February 2013
Actual Study Completion Date : February 2013

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. Tumor size of hepatic and/or lung metastases, as measured with tomodensitometry (RECIST 1.1 criteria) [ Time Frame: from Month 1 to Month 9 ]

Secondary Outcome Measures :
  1. 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 ]
  2. Sonography : assessment of vascular micro-circulation with contrast injection, [ Time Frame: Month 1 to Month 9 ]
  3. Immune cell reconstitution will be assessed through measuring rate of regulatory T-cell reconstitution, [ Time Frame: day 7 to 28 ]
  4. Clinical Exam (WHO-CTC), Vital Signs, Adverse events [ Time Frame: day 1 to 28 ]
  5. Laboratory test: hepatic function, immune function, haematology [ Time Frame: day 1 to 28 ]

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00986518

Service hépato-gastro-enterologie, Pitié-Salpêtrière Hospital
Paris, France, 75013
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Principal Investigator: David Klatzmann, MD, PhD Pitié-Salpêtrière Hospital

Responsible Party: Assistance Publique - Hôpitaux de Paris Identifier: NCT00986518     History of Changes
Other Study ID Numbers: P080601
First Posted: September 30, 2009    Key Record Dates
Last Update Posted: November 25, 2013
Last Verified: September 2013

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Advanced Colorectal Cancer
Hepatic and/or lung metastasis
Adaptive autologous cell immunotherapy
T- regulatory lymphocyte depletion
Neo-adjuvant reduced intensity chemotherapeutic conditioning

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases