Immunotherapy of Hepatocellular Carcinoma With Gamma Delta T Cells (ICAR)

Immunotherapy of Hepatocellular Carcinoma by Hepatic Intra Arterial Injection of Autologous Gamma-delta T Lymphocytes: A Phase I Study

For most patients with hepatocellular carcinoma, surgery or other curative procedures are not possible and only palliative measures could be applied (chemoembolization, targeted drugs, best supportive cares, etc). In the ICAR study, increasing doses of a cell therapy product will be evaluated in patients in a palliative setting. All patients will have one hepatic intra-arterial injection of immunological cells (gamma-delta T lymphocytes) and will be evaluated for safety.

Study Overview

• Status: Terminated
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Other: T gamma delta lymphocytes

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Rennes, France, 35000
    • Unité de Thérapie Cellulaire, Laboratoire de Cytogénétique et Biologie Cellulaire, CHU Rennes
  • Rennes, France, 35042
    • Département d'Oncologie Médicale - CRLCC Eugène Marquis
  • Rennes, France
    • Service de Chirugie Viscérale - Hôpital de Pontchaillou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult over 18
• Hepatocellular carcinoma histologically proven, with at least one measurable tumor
• Non operable tumor
• Alfa foeto protein > 400 ng/ml
• Other treatments (surgery, chemoembolization) non indicated
• Chemoembolization non indicated due to good performance status (WHO 1) or to tumor volume
• Performance status WHO < 2
• Life expectancy > 3 months

Non inclusion Criteria:

• Extra hepatic metastases
• Severe hepatopathy (Child B or C)
• Virus B or C chronic hepatitis
• Chronic cardiac failure
• Uncontrolled severe infectious disease
• Other cancer, if not considered as cured
• Positive serology for HIV or HTLV
• Leucocytes < 3000/mm3 or neutrophils < 1500/mm3
• Platelets < 80000/mm3
• Serum creatinine > 110 µmol/L
• Bilirubin > 35 µmol/L
• AST, ALT, alkaline phosphatase > 5N
• Current immunosuppressive treatment
• Impossibility to comply with scheduled follow-up
• Anatomical situation not permitting the selective injection of the product of cell therapy
• Pregnant or breastfeeding woman, or not using adequate effective contraceptive method

Exclusion Criterion:

• Insufficient number of gamma delta lymphocytes after expansion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Single hepatic intra arterial administration of 500 millions T gamma delta lymphocytes	Other: T gamma delta lymphocytes; Single hepatic intra arterial administration of increasing doses of T gamma delta lymphocytes
Experimental: 2; Single hepatic intra arterial administration of 1000 millions T gamma delta lymphocytes	Other: T gamma delta lymphocytes; Single hepatic intra arterial administration of increasing doses of T gamma delta lymphocytes
Experimental: 3; Single hepatic intra arterial administration of 2000 millions T gamma delta lymphocytes	Other: T gamma delta lymphocytes; Single hepatic intra arterial administration of increasing doses of T gamma delta lymphocytes
Experimental: 4; Single hepatic intra arterial administration of 4000 millions T gamma delta lymphocytes	Other: T gamma delta lymphocytes; Single hepatic intra arterial administration of increasing doses of T gamma delta lymphocytes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Onset of: thrombosis of hepatic artery, grade 4 liver toxicity, or grade 3 or more allergic, neurological, dermatological, infectious, or respiratory reaction	Within 14 days after treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Onset of clinical, biological signs or images evocative of lymphocyte-induced tumor cytotoxicity and/or of a persistence of gamma-delta T cells in peripheral blood. Tumor response will be evaluated with the RECIST criteria.	3 months

Collaborators and Investigators

• Sponsor: Rennes University Hospital
• Collaborators: Innate Pharma
• Investigators: Principal Investigator: Jean-Luc RAOUL, MD, PhD, CRLCC Eugène Marquis, Rennes

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): January 1, 2009
• Study Completion (Actual): January 1, 2009

Study Registration Dates

• First Submitted: November 21, 2007
• First Submitted That Met QC Criteria: November 21, 2007
• First Posted (Estimate): November 22, 2007

Study Record Updates

• Last Update Posted (Estimate): June 22, 2012
• Last Update Submitted That Met QC Criteria: June 21, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: cell therapy; T lymphocytes; hepatic intra-arterial injection
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: ID RCB 2007-A00249-44; CIC 0203/074; LOC 06/07