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Tumor Infiltrating Lymphocytes Adjuvant Therapy of Melanoma (TIL)

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ClinicalTrials.gov Identifier: NCT00200577
Recruitment Status : Completed
First Posted : September 20, 2005
Last Update Posted : June 1, 2017
Sponsor:
Information provided by (Responsible Party):
Nantes University Hospital

Tracking Information
First Submitted Date  ICMJE September 12, 2005
First Posted Date  ICMJE September 20, 2005
Last Update Posted Date June 1, 2017
Study Start Date  ICMJE May 2005
Actual Primary Completion Date March 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 30, 2008)
  • Determination of the duration of the relapse-free interval. [ Time Frame: 5 years ]
  • Physical examination, every 2 months until M18 then every 3 months until M36 then every 4 months up to 5 years, then once per year with a clinical examination only. [ Time Frame: every 2 months until M18then every 3 months until M36 then every 4 months up to 5 years ]
  • Abdominal echography will be performed at the screening visit, M4, M8, M12 and then every 6 months until 5ans. [ Time Frame: M4, M8, M12 and then every 6 months until 5ans. ]
  • CT-Scan will be performed before the first administration of study treatment (at the time of screening visit), every 6 months during 2 years and then every years up to 5 years. [ Time Frame: every 6 months during 2 years and then every years up to 5 years. ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 12, 2005)
  • Determination of the duration of the relapse-free interval.
  • Physical examination, every 2 months until M18 then every 3 months until M36 then every 4 months up to 5 years, then once per year with a clinical examination only.
  • Abdominal echography will be performed at the screening visit, M4, M8, M12 and then every 6 months until 5ans.
  • CT-Scan will be performed before the first administration of study treatment (at the time of screening visit), every 6 months during 2 years and then every years up to 5 years.
Change History Complete list of historical versions of study NCT00200577 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 30, 2008)
  • Determine of overall survival [ Time Frame: 5 years ]
  • To define safety and toxicity of TIL/IL2 treatment [ Time Frame: 5 years ]
  • Evaluation of immunological responses [ Time Frame: M0, J56, M12 ]
  • Analysis of the clinical, biological and histological factors on the survival of the patients [ Time Frame: at inclusion and each month ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 12, 2005)
  • - Determine of overall survival
  • - To define safety and toxicity of TIL/IL2 treatment
  • - Evaluation of immunological responses
  • - Analysis of the clinical, biological and histological factors on the survival of the patients
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Tumor Infiltrating Lymphocytes Adjuvant Therapy of Melanoma
Official Title  ICMJE TIL (Tumor Infiltrating Lymphocytes) and IL2 (Interleukin 2) Versus Abstention as Adjuvant Treatment in Melanoma With Only One Invaded Lymphnode After Lymphnodes Excision
Brief Summary The objective of this multicentric Phase III study is to confirm the results of the phase I-II study (Dreno B & Al. Cancer Immunol Immunother 2002; 51: 539-456) which demonstrated the preventive effect of a treatment by TIL (Tumor Infiltrating Lymphocytes) combined with IL2 (Interleukin 2; low dose injected subcutaneously) on the metastatic relapse in the stage III melanoma patients with only one invaded lymphnode.
Detailed Description In this open, multicentric (Grenoble, Montpellier, Nantes, Angers, Caen, Le Mans, Poitiers, Rennes, Tours) randomized study, selected patients with only one invaded lymphnode confirmed by anatomopathological exam will be randomized to one of the following arms: 1-Control group: patients of this group will not receive any treatment and will have the same clinical follow-up as the treated group. 2- TIL-IL2 group: treated patients will receive two injections of TIL combined with IL2. Tumor Infiltrating Lymphocytes will be obtained from a small piece of tumour tissue removed from the invaded lymphnode after surgery. TIL will be grown in larger number in laboratory during 6 weeks. Patients randomized in treatment arm will receive two injection of TIL (the first about 6 and the second about 10 weeks post-surgery). Administration of TIL will be combined with a low dose of IL2 (6 million U.I. per day) injected subcutaneously from J1 to J5 and J8 to J12 following the day of TIL infusion. The same dose and duration of IL2 treatment will be used for the second injection of TIL performed one month later. After 2 months adjuvant therapy, patients received no other treatment. Only a regular follow-up was performed.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Melanoma
Intervention  ICMJE Drug: TIL + IL2
Patients are treated with 2 injections Of TIL (1st injection M1 and the second M2)The received concomitant IL2 at M1 and M2 on days Jo (injection TIL) to J5 and J8 to J12
Study Arms  ICMJE
  • Experimental: TIL+IL2
    TIL + IL2
    Intervention: Drug: TIL + IL2
  • No Intervention: control
    Patients are not treated
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 12, 2005)
70
Original Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 2012
Actual Primary Completion Date March 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Melanoma stage III (regional lymph node recurrence). Will be selected the patients with only one invaded lymph node confirmed by anatomopathological exam after lymph nodes excision.
  • Absence of visceral metastases verified by physical examination, chest radiography, liver echography and brain-chest-liver CT-Scan.
  • Age < 75 years, both genders
  • ECOG 0-2, Karnofsky > 80%.
  • Negative pregnancy test performed at the screening visit for fertile women.
  • The potentially fertile women must use an oral contraception or an intra-uterine device (IUD) until three months following the last injection of the study treatment.
  • The patients must have fully recovered from surgery.
  • HIV 1/2: The patients must be negative for antibodies HIV 1 and HIV 2 and for Ag P24 or DGV HIV.
  • HBV: The patients must be negative for the antigen, but can be positive for the antibodies but with a negative DNA PCR.
  • HCV: The patients must be negative for the antibodies.
  • HTLV ½: The patients must be negative for the antibodies.
  • Following laboratory results:

    • Hemoglobin: ≥ 10 g/dl
    • WBC: ≥ 4000/µl
    • Lymphocytes: ≥ 700/µl
    • Platelet count: ≥ 100.000/µl
    • Serum creatinine: < 2.0 mg/dl or £ 177 mmol/l
    • Serum Bilirubin: < 2.0 mg/dl or £ 34.2 mmol/l
    • ASAT and ALAT: < 2.5 x the upper limit of normal.

Exclusion criteria:

  • Patient with more than one invaded lymph node confirmed by anatomopathological exam.
  • Presence of melanoma metastases discovered by clinical or radiological examination at the screening visit.
  • Patients must not have received any Chemotherapy, immunotherapy or radiotherapy within the preceding 4 weeks (6 weeks since prior nitrosurea and mitomycin C therapies).
  • Presence of cardiac affections (congestive cardiac insufficiency, coronaropathy, not controlled HTA).
  • Any serious active medical illnesses, for example: Active systemic infections requiring of antibiotics, coagulation disorders or any other condition which requires concomitant medications not allowed during this study.
  • Presence of the second active cancer other than surgically cured non-melanoma skin cancer or cervical carcinoma in-situ.
  • Any affection requiring a systemic corticotherapy or a treatment by Interferon A.
  • Any active auto-immune disease including the insulin-dependent diabetes or a immunodeficiency. The vitiligo is not an exclusion criteria.
  • Thyroid dysfunction not responsive to therapy.
  • Positive Serology for HIV, HVB, HVC or HTLV1/2.
  • Woman pregnant or nursing or without an effective contraception.
  • Incapacity to give written consent.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 75 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00200577
Other Study ID Numbers  ICMJE BRD/04/01-D
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Nantes University Hospital
Study Sponsor  ICMJE Nantes University Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Brigitte DRENO, MD Nantes University Hospital
PRS Account Nantes University Hospital
Verification Date May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP