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Metastatic MelanomaPhase 3TILNCT02278887

Study Comparing TIL to Standard Ipilimumab in Patients With Metastatic Melanoma

A Phase 3 study testing Translational research, Cyclophosphamide and Fludarabine in people with Metastatic Melanoma, run by The Netherlands Cancer Institute at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

In this randomized controlled phase III study the investigators will evaluate whether TIL infusion preceded by non-myeloablative chemotherapy and followed by high dose bolus interleukin-2 can result in an improved progression free survival when randomly compared to ipilimumab in 168 stage IV melanoma patients. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Metastatic Melanoma
What is being tested?
Translational research, Cyclophosphamide and Fludarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
168 participants
Where
2 sitesin 2 countries
Study dates
23 Sep 2014to 31 Dec 2023
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 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed unresectable AJCC stage III or stage IV melanoma
  • Patients must have metastatic melanoma with a resectable metastatic lesion(s) of sufficient size (≥ 2-3 cm in total) and must be willing to undergo such a resection for experimental purposes.
  • Patients should have received maximum one line of systemic therapy (except for ipilimumab) for unresectable or metastatic melanoma.[
  • Patients must be ≥ 18 years and ≤ 75 years of age and must have measurable disease by CT or MRI per RECIST 1.1 criteria (in addition to the resected lesion).
  • Patients must have a clinical performance status of ECOG 0 or 1.
  • Patients of both genders must be willing to practice a highly effective method of birth control during treatment and for four months after receiving the preparative regimen.
  • Patients must be able to understand and sign the Informed Consent document.

Who cannot join

  • Life expectancy of less than three months.
  • Patients with metastatic ocular/ mucosal or other non-cutaneous melanoma.
  • Adjuvant treatment with ipilimumab within 6 months prior to randomization.
  • Requirement for immunosuppressive doses of systemic corticosteroids (>10 mg/day prednisone or equivalent) or other immunosuppressive drugs within the last 3 weeks prior to randomization.
  • Patients who have a more than two CNS metastases.
  • Patients who have any CNS lesion that is symptomatic, greater than 1 cm in diameter or show significant surrounding edema on MRI scan will not be eligible until they have been treated and demonstrated no clinical or radiologic CNS progression for at least 2 months.
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  • All patients' toxicities due to prior non-systemic treatment must have recovered to a grade 1 or less. Patients may have undergone minor surgical procedures or focal palliative radiotherapy (to non-target lesions) within the past 4 weeks, as long as all toxicities have recovered to grade 1 or less.
  • Women who are pregnant or breastfeeding, because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
  • Any active systemic infections, coagulation disorders or other active major medical illnesses.
  • Any autoimmune disease

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

Denmark1 site

  • CCIT Department of Oncology and Haematology Herlev Hospital

    Copenhagen

Other trials in Denmark

Netherlands1 site

  • Netherlands Cancer Institute

    Amsterdam, North Holland, 1066CX

Other trials in Netherlands

About this study

Official title: Randomized Phase III Study Comparing a Non-myeloablative Lymphocyte Depleting Regimen of Chemotherapy Followed by Infusion of Tumor Infiltrating Lymphocytes and Interleukin-2 to Standard Ipilimumab Treatment in Metastatic Melanoma

In this randomized controlled phase III study the investigators will evaluate whether TIL infusion preceded by non-myeloablative chemotherapy and followed by high dose bolus interleukin-2 can result in an improved progression free survival when randomly compared to ipilimumab in 168 stage IV melanoma patients. A health technology assessment (HTA) will be performed to evaluate the impact of the TIL treatment on patients and organizational processes and cost-effectivity.

Read the detailed description

In this randomized controlled phase III study the investigators will evaluate whether TIL infusion preceded by non-myeloablative chemotherapy and followed by high dose bolus interleukin-2 can result in an improved progression free survival when randomly compared to ipilimumab in 168 stage IV melanoma patients. A health technology assessment (HTA) will be performed to evaluate the impact of the TIL treatment on patients and organizational processes and cost-effectivity. This will be done via questionnaires at baseline, just after treatment and during follow-up. Also healthcare providers will be interviewed after 6 months after starting the trial.

Being tested
Translational research, Cyclophosphamide, Fludarabine, Interleukin-2, Ipilimumab infusion
Keywords
melanoma, TIL treatment, tumor infiltrating lymphocytes, ipilimumab, interleukin 2, non-myeloablative, randomization
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Translational researchProcedure or surgery

    Also called tumor tissue, blood

    Before during and at progression/regression biopsies and blood will be taken for translational research

  • CyclophosphamideDrug

    Also called chemotherapy

    The patient receives 2 days cyclophosphamide via IV to deplete T-cells.

  • FludarabineDrug

    Also called chemotherapy

    The patient receives 5 days fludarabine via IV to deplete T-cells.

  • Interleukin-2Drug

    Also called Proleukin

    After infusion of the TIL, the patient receives IL-2 to keep the TIL active.

  • Ipilimumab infusionDrug

    Also called standard treatment

    In arm A patients will be treated with 4 infusion of ipilimumab

Study groups in NCT02278887
Study groupRoleWhat they receive
IpilimumabActive comparator4 cycles of ipilimumab treatment, the standard treatment
Receives: Procedure: Translational research; Drug: Ipilimumab infusion
TIL treatmentExperimentalnon-myeloablative lymphocyte depleting regimen of chemotherapy followed by infusion of tumor infiltrating lymphocytes and interleukin-2
Receives: Procedure: Translational research; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Interleukin-2

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression free survival

    Progression free survival according to RECIST 1.1

    Measured: 3 years

Secondary outcomes (1)

  1. Immune related progression free survival

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Oct 2014 (estimated)
  2. Study start23 Sep 2014
  3. Primary completionSep 2022
  4. Study completion31 Dec 2023

Resources

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
168 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02278887
Sponsor's protocol ID
M14TIL
Acronym
TIL
Status last verified
Mar 2025
First submitted
3 Jun 2014
Last updated
10 Mar 2025
Results posted
No
Data monitoring committee
Yes

Publications

  • Ten Ham RMT, Rohaan MW, Egeler M, Menezes R, Holz Borch T, Kessels R, Jedema I, Nuijen B, Nijenhuis CM, van de Poll-Franse LV, Geukes Foppen MH, Lindenberg M, Mansfield Noringriis I, Monberg TJ, Donia M, van Harten W, Svane IM, Haanen JBAG, Retel VP. Health-related quality of life of patients with metastatic melanoma treated with tumor-infiltrating lymphocytes compared with ipilimumab in a randomized phase III trial. Ann Oncol. 2025 Oct;36(10):1154-1165. doi: 10.1016/j.annonc.2025.06.005. Epub 2025 Jun 18.

    PubMed 40541863

  • Tas L, Weitemeyer MB, Rohaan MW, Borch TH, van Akkooi ACJ, Wouters MWJM, Hartemink KJ, Schrage YM, Kuijpers A, Kok NFM, van Zon M, Jedema I, Nijenhuis CM, Nuijen B, Hansen M, Voermans C, Klobuch S, Seijkens TTP, Lalezari F, Met O, Donia M, Svane IM, Haanen JBAG, Holmich LR, van Houdt WJ. Surgical considerations for tumour-infiltrating lymphocyte therapy in melanoma: results from a randomized phase III trial. Br J Surg. 2025 May 31;112(6):znaf090. doi: 10.1093/bjs/znaf090.

    PubMed 40474841

  • Rohaan MW, Borch TH, van den Berg JH, Met O, Kessels R, Geukes Foppen MH, Stoltenborg Granhoj J, Nuijen B, Nijenhuis C, Jedema I, van Zon M, Scheij S, Beijnen JH, Hansen M, Voermans C, Noringriis IM, Monberg TJ, Holmstroem RB, Wever LDV, van Dijk M, Grijpink-Ongering LG, Valkenet LHM, Torres Acosta A, Karger M, Borgers JSW, Ten Ham RMT, Retel VP, van Harten WH, Lalezari F, van Tinteren H, van der Veldt AAM, Hospers GAP, Stevense-den Boer MAM, Suijkerbuijk KPM, Aarts MJB, Piersma D, van den Eertwegh AJM, de Groot JB, Vreugdenhil G, Kapiteijn E, Boers-Sonderen MJ, Fiets WE, van den Berkmortel FWPJ, Ellebaek E, Holmich LR, van Akkooi ACJ, van Houdt WJ, Wouters MWJM, van Thienen JV, Blank CU, Meerveld-Eggink A, Klobuch S, Wilgenhof S, Schumacher TN, Donia M, Svane IM, Haanen JBAG. Tumor-Infiltrating Lymphocyte Therapy or Ipilimumab in Advanced Melanoma. N Engl J Med. 2022 Dec 8;387(23):2113-2125. doi: 10.1056/NEJMoa2210233.

    PubMed 36477031

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Translational research, Cyclophosphamide and Fludarabine in people with Metastatic Melanoma, run by The Netherlands Cancer Institute at 2 sites in 2 countries.

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 7 inclusion and 10 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 10 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Denmark, Netherlands. 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?

Progression free survival (time frame: 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02278887, which also lists 3 linked publications.

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 10 Mar 2025.

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