MelanomaPhase 3TILNCT00200577
Tumor Infiltrating Lymphocytes Adjuvant Therapy of Melanoma
A Phase 3 study testing TIL + IL2 in people with Melanoma, run by Nantes University Hospital at 9 sites in France.
Trial 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… Read more about this study
- Who is it for?
- Ages Up to 75 years
- Conditions the study is for
- Melanoma
- What is being tested?
- TIL + IL2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 9 sitesFrance
- Study dates
- May 2005to Mar 2012
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
France9 sites
CHU Angers
Angers
CHU Caen
Caen
Grenoble University Hospital
Grenoble
CH Le Mans
Le Mans
Montpellier University Hospital
Montpellier
Nantes University Hospital
Nantes, 44093
CHU Poitiers
Poitiers
CHU Rennes
Rennes
CHRU Tours
Tours
About this study
Official title: TIL (Tumor Infiltrating Lymphocytes) and IL2 (Interleukin 2) Versus Abstention as Adjuvant Treatment in Melanoma With Only One Invaded Lymphnode After Lymphnodes Excision
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.
Read the 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.
- Conditions
- Melanoma
- Being tested
- TIL + IL2
- Keywords
- Adjuvant therapy, immunotherapy, TIL, melanoma
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TIL + IL2Drug
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 group | Role | What they receive |
|---|---|---|
| TIL+IL2 | Experimental | TIL + IL2 Receives: Drug: TIL + IL2 |
| control | No intervention | Patients are not treated |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determination of the duration of the relapse-free interval.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: every 6 months during 2 years and then every years up to 5 years.
Secondary outcomes (4)
Determine of overall survival
Measured: 5 years
To define safety and toxicity of TIL/IL2 treatment
Measured: 5 years
Evaluation of immunological responses
Measured: M0, J56, M12
Analysis of the clinical, biological and histological factors on the survival of the patients
Measured: at inclusion and each month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2005 (estimated)
- Study startMay 2005
- Primary completionMar 2012
- Study completionMar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by Nantes University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nantes University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Brigitte DRENO, MD, Principal investigator, Nantes University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00200577
- Sponsor's protocol ID
- BRD/04/01-D
- Acronym
- TIL
- Status last verified
- May 2017
- First submitted
- 12 Sep 2005
- Last updated
- 1 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TIL (Tumor Infiltrating Lymphocytes) and IL2 (Interleukin 2) Versus Abstention as Adjuvant Treatment in Melanoma With Only One Invaded Lymphnode After Lymphnodes Excision
- ClinicalTrials.gov ID
- NCT00200577
- Acronym / sponsor ID
- TIL / BRD/04/01-D
- Conditions
- Melanoma
- Keywords
- Adjuvant therapy, immunotherapy, TIL, melanoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Nantes University HospitalUniversity, hospital or other
- Study start
- May 2005
- Primary completion
- Mar 2012 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 20 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TIL+IL2 | Experimental | Drug: TIL + IL2TIL + IL2 |
| control | No intervention | –Patients are not treated |
Who may qualify
- Ages
- Up to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (19 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TIL + IL2Patients 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 | Drug | TIL+IL2 |
Primary outcome
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.
4 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brigitte DRENO, MD principal investigator
Nantes University Hospital
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing TIL + IL2 in people with Melanoma, run by Nantes University Hospital at 9 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determination of the duration of the relapse-free interval. (time frame: 5 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2017.