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

• ClinicalTrials.gov Identifier: NCT02278887
• Recruitment Status: Active, not recruiting
• First Posted: October 30, 2014
• Last Update Posted: November 15, 2023
• Sponsor: The Netherlands Cancer Institute
• Collaborator: Copenhagen University Hospital at Herlev
• Information provided by (Responsible Party): The Netherlands Cancer Institute

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.

Condition or disease	Intervention/treatment	Phase
Metastatic Melanoma	Procedure: Translational research; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Interleukin-2; Drug: Ipilimumab infusion	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 168 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: September 23, 2014
• Actual Primary Completion Date: September 2022
• Estimated Study Completion Date: June 2027

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Ipilimumab; 4 cycles of ipilimumab treatment, the standard treatment	Procedure: Translational research; Before during and at progression/regression biopsies and blood will be taken for translational research; Other Names: tumor tissue; blood; Drug: Ipilimumab infusion; In arm A patients will be treated with 4 infusion of ipilimumab; Other Name: standard treatment
Experimental: TIL treatment; non-myeloablative lymphocyte depleting regimen of chemotherapy followed by infusion of tumor infiltrating lymphocytes and interleukin-2	Procedure: Translational research; Before during and at progression/regression biopsies and blood will be taken for translational research; Other Names: tumor tissue; blood; Drug: Cyclophosphamide; The patient receives 2 days cyclophosphamide via IV to deplete T-cells.; Other Name: chemotherapy; Drug: Fludarabine; The patient receives 5 days fludarabine via IV to deplete T-cells.; Other Name: chemotherapy; Drug: Interleukin-2; After infusion of the TIL, the patient receives IL-2 to keep the TIL active.; Other Name: Proleukin

Outcome Measures

Primary Outcome Measures :

1. Progression free survival [ Time Frame: 3 years ]
   Progression free survival according to RECIST 1.1

Secondary Outcome Measures :

1. Immune related progression free survival [ Time Frame: 3 years ]

Other Outcome Measures:

1. Safety [ Time Frame: 3 years ]
   Adverse events will be assessed during treatment and follow-up

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Denmark

CCIT Department of Oncology and Haematology Herlev Hospital

Copenhagen, Denmark

Netherlands

Netherlands Cancer Institute

Amsterdam, NH, Netherlands, 1066CX

Sponsors and Collaborators

The Netherlands Cancer Institute

Copenhagen University Hospital at Herlev

Investigators

• Principal Investigator: John B.A.G. Haanen, Prof.; The Netherlands Cancer Institute

More Information

• Responsible Party: The Netherlands Cancer Institute
• ClinicalTrials.gov Identifier: NCT02278887
• Other Study ID Numbers: M14TIL
• First Posted: October 30, 2014
• Last Update Posted: November 15, 2023
• Last Verified: November 2023

Keywords provided by The Netherlands Cancer Institute:

melanoma; TIL treatment; tumor infiltrating lymphocytes; ipilimumab; interleukin 2; non-myeloablative; randomization

Additional relevant MeSH terms:

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Cyclophosphamide; Fludarabine; Ipilimumab; Interleukin-2; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents