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

NCT00986518 | Completed Phase 1 DMC

• 1 other identifier: P080601
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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).

Conditions

Colorectal Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

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

  from Month 1 to Month 9

Secondary Outcomes (5)

• MRI : Assessment of tumor necrosis, cellularity and morphological criteria RECIST 1.1 (functional criteria following injection : DCEMRI and diffusion MRI)

  Month 1 to Month 9

• Sonography : assessment of vascular micro-circulation with contrast injection,

  Month 1 to Month 9

• Immune cell reconstitution will be assessed through measuring rate of regulatory T-cell reconstitution,

  day 7 to 28

• Clinical Exam (WHO-CTC), Vital Signs, Adverse events

  day 1 to 28

• Laboratory test: hepatic function, immune function, haematology

  day 1 to 28

Study Arms (1)

adaptive cell immunotherapy

EXPERIMENTAL

Biological: Adaptive autologous cell immunotherapy

Interventions

Adaptive autologous cell immunotherapy BIOLOGICAL

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.

adaptive cell immunotherapy

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Service hépato-gastro-enterologie, Pitié-Salpêtrière Hospital

Paris, 75013, France

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• David Klatzmann, MD, PhD

  Pitié-Salpêtrière Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2009
• First Posted: September 30, 2009
• Study Start: October 1, 2012
• Primary Completion: February 1, 2013
• Study Completion: February 1, 2013
• Last Updated: November 25, 2013

Record last verified: 2013-09

Locations

FR (1)