Tumor Infiltrating Lymphocytes Adjuvant Therapy of Melanoma - Full Text View

Sponsored by:	Nantes University Hospital
Information provided by:	Nantes University Hospital
ClinicalTrials.gov Identifier:	NCT00200577

Purpose

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 interleukin 2 (low dose injected subcutaneously) on the metastatic relapse in the stage III melanoma patients with only one invaded lymphnode.

Condition	Intervention	Phase
Melanoma	Drug: TIL + IL2	Phase III

MedlinePlus related topics: Cancer Melanoma

Drug Information available for: Interleukin-2

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment
Official Title:	TIL (Tumor Infiltrating Lymphocytes) and Interleukin 2 Versus Abstention as Adjuvant Treatment in Melanoma With Only One Invaded Lymphnode After Lymphnodes Excision

Further study details as provided by Nantes University Hospital:

Primary Outcome Measures:

Determination of the duration of the relapse-free interval. [ Time Frame: 5 years ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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. ] [ Designated as safety issue: No ]
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. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Determine of overall survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
To define safety and toxicity of TIL/IL2 treatment [ Time Frame: 5 years ] [ Designated as safety issue: No ]
Evaluation of immunological responses [ Time Frame: M0, J56, M12 ] [ Designated as safety issue: No ]
Analysis of the clinical, biological and histological factors on the survival of the patients [ Time Frame: at inclusion and each month ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	70
Study Start Date:	May 2005
Estimated Study Completion Date:	June 2011
Estimated Primary Completion Date:	June 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
TIL+IL2: Experimental TIL + IL2	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
control: No Intervention Patients are not treated

Detailed Description:

In this open, multicentric (Grenoble, Montpellier, Nantes) 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.

Eligibility

Ages Eligible for Study:	up to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00200577

Contacts

Contact: Brigitte DRENO, MD	00 33 (0) 2 40 08 31 16	bdreno@wanadoo.fr
Contact: Amir KHAMMARI, MPh	00 33 (0) 2 40 08 32 80	akhammari@chu-nantes.fr

Locations

France
Nantes University Hospital	Recruiting
Nantes, France, 44093
Contact: Brigitte DRENO, MD 00 33 (0) 2 40 08 31 16 bdreno@wanadoo.fr
Contact: Amir KHAMMARI 00 33 (0) 2 40 08 32 80 akhammari@chu-nantes.fr
Principal Investigator: Brigitte DRENO, MD
Grenoble University Hospital	Recruiting
grenoble, France
Contact: Marie Thérèse LECCIA, MD mt.leccia@chu-grenoble.fr
Principal Investigator: MT LECCIA, MD
Montpellier University Hospital	Recruiting
Montpellier, France
Contact: Bernard GUILLOT, MD bguillot@chu-montpellier.fr
Principal Investigator: Bernard Guillot, MD
Sub-Investigator: Olivier Dereure, MD

Sponsors and Collaborators

Nantes University Hospital

Investigators

Principal Investigator:

Brigitte DRENO, MD

Nantes University Hospital

More Information

Responsible Party:	nantes University hospital ( Pr brigitte DRENO )
Study ID Numbers:	BRD/04/1-D
Study First Received:	September 12, 2005
Last Updated:	July 18, 2008
ClinicalTrials.gov Identifier:	NCT00200577
Health Authority:	France: Afssaps - French Health Products Safety Agency

Keywords provided by Nantes University Hospital:

Adjuvant therapy
immunotherapy
TIL
melanoma

Study placed in the following topic categories:

Neuroectodermal Tumors
Interleukin-2
Nevus, Pigmented
Neoplasms, Germ Cell and Embryonal

Neuroepithelioma
Nevus
Neuroendocrine Tumors
Melanoma

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on January 16, 2009