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Study Comparing TIL to Standard Ipilimumab in Patients With Metastatic Melanoma (TIL)

Primary Purpose

Metastatic Melanoma

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Translational research
Cyclophosphamide
Fludarabine
Interleukin-2
Ipilimumab infusion
Sponsored by
The Netherlands Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Melanoma focused on measuring melanoma, TIL treatment, tumor infiltrating lymphocytes, ipilimumab, interleukin 2, non-myeloablative, randomization

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • 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

Sites / Locations

  • CCIT Department of Oncology and Haematology Herlev Hospital
  • Netherlands Cancer Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Ipilimumab

TIL treatment

Arm Description

4 cycles of ipilimumab treatment, the standard treatment

non-myeloablative lymphocyte depleting regimen of chemotherapy followed by infusion of tumor infiltrating lymphocytes and interleukin-2

Outcomes

Primary Outcome Measures

Progression free survival
Progression free survival according to RECIST 1.1

Secondary Outcome Measures

Immune related progression free survival

Full Information

First Posted
June 3, 2014
Last Updated
July 8, 2022
Sponsor
The Netherlands Cancer Institute
Collaborators
Copenhagen University Hospital at Herlev
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1. Study Identification

Unique Protocol Identification Number
NCT02278887
Brief Title
Study Comparing TIL to Standard Ipilimumab in Patients With Metastatic Melanoma
Acronym
TIL
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 23, 2014 (Actual)
Primary Completion Date
September 2022 (Anticipated)
Study Completion Date
September 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The Netherlands Cancer Institute
Collaborators
Copenhagen University Hospital at Herlev

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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. A health technology assessment (HTA) will be performed to evaluate the impact of the TIL treatment on patients and organizational processes and cost-effectivity.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Melanoma
Keywords
melanoma, TIL treatment, tumor infiltrating lymphocytes, ipilimumab, interleukin 2, non-myeloablative, randomization

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
168 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ipilimumab
Arm Type
Active Comparator
Arm Description
4 cycles of ipilimumab treatment, the standard treatment
Arm Title
TIL treatment
Arm Type
Experimental
Arm Description
non-myeloablative lymphocyte depleting regimen of chemotherapy followed by infusion of tumor infiltrating lymphocytes and interleukin-2
Intervention Type
Procedure
Intervention Name(s)
Translational research
Other Intervention Name(s)
tumor tissue, blood
Intervention Description
Before during and at progression/regression biopsies and blood will be taken for translational research
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
chemotherapy
Intervention Description
The patient receives 2 days cyclophosphamide via IV to deplete T-cells.
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
chemotherapy
Intervention Description
The patient receives 5 days fludarabine via IV to deplete T-cells.
Intervention Type
Drug
Intervention Name(s)
Interleukin-2
Other Intervention Name(s)
Proleukin
Intervention Description
After infusion of the TIL, the patient receives IL-2 to keep the TIL active.
Intervention Type
Drug
Intervention Name(s)
Ipilimumab infusion
Other Intervention Name(s)
standard treatment
Intervention Description
In arm A patients will be treated with 4 infusion of ipilimumab
Primary Outcome Measure Information:
Title
Progression free survival
Description
Progression free survival according to RECIST 1.1
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Immune related progression free survival
Time Frame
3 years
Other Pre-specified Outcome Measures:
Title
Safety
Description
Adverse events will be assessed during treatment and follow-up
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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. 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John B.A.G. Haanen, Prof.
Organizational Affiliation
The Netherlands Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
CCIT Department of Oncology and Haematology Herlev Hospital
City
Copenhagen
Country
Denmark
Facility Name
Netherlands Cancer Institute
City
Amsterdam
State/Province
NH
ZIP/Postal Code
1066CX
Country
Netherlands

12. IPD Sharing Statement

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Study Comparing TIL to Standard Ipilimumab in Patients With Metastatic Melanoma

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