TIL-ACT After NMA Chemo With IL-2 and Nivo Rescue in Metastatic Melanoma (mMEL)
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|ClinicalTrials.gov Identifier: NCT03475134|
Recruitment Status : Recruiting
First Posted : March 23, 2018
Last Update Posted : March 26, 2018
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Melanoma||Other: TIL Drug: Cyclophosphamide Drug: Fludarabine Drug: Interleukin-2 Drug: Nivolumab||Phase 1|
The objective of the trial is to define the feasibility and safety of TIL-ACT in metastatic melanoma patients. In addition, the feasibility and safety of nivolumab rescue in patients with advanced metastatic disease is examined.
Study treatment will begin with intravenous non-myeloablative (NMA) lymphodepleting chemotherapy composed by fludarabine and cyclophosphamide. Both treatments will be started on the same day. Fludarabine will be administered for five days, and cyclophosphamide for two days. TILs will be infused intravenously over a period of 20-30 minutes. Two to three hours after the infusion of TILs, optional IL-2 will be started as a bolus administration every eight hours, for a maximum of eight doses. In order to avoid profound and long-lasting neutropenia, pegfilgrastim will be given subcutaneously. Supportive care will be given during the recovery phase from immune depletion and IL-2 therapy.
Nivolumab rescue will be initiated for eligible patients. For all patients, the first on-treatment radiological assessment will be performed 30 days after the TIL infusion, and then at month 3, and then every 12 weeks for the first 3 years of follow-up and every 4-6 months for the next 2 years, until progression.
Two Positron Emission Tomography-Computed Tomography (PET-CT) (18FDG (Fludeoxyglucose (F18)) and 68Ga-NODAGA-RGD ((68)Ga-labelled NOTA-conjugated RGD peptide) will be performed at baseline, following chemotherapy, and between 22-30 days after the TIL infusion.
The safety assessment for TIL-ACT (TLT (treatment-limiting toxicity) period) will extend from day -7 (when NMA chemo starts) till 30 days after TIL infusion.
The first three evaluable patients will be enroled no less than 2 weeks apart from each other. An interim analysis of safety at our center will be performed at the completion of the TLT period of the third evaluable patient.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Study to Assess Feasibility and Safety of Adoptive Transfer of Autologous Tumor-Infiltrating Lymphocytes in Combination With Interleukin-2 Followed by Nivolumab Rescue for Advanced Metastatic Melanoma|
|Actual Study Start Date :||February 21, 2018|
|Estimated Primary Completion Date :||June 1, 2024|
|Estimated Study Completion Date :||June 1, 2024|
Experimental: TIL-ACT +/- Nivolumab rescue
Non-myeloablative lymphodepleting chemotherapy (cyclophosphamide and fludarabine), Tumor Infiltrating Lymphocyte (TIL)-Adoptive Cell Therapy (ACT), Interleukin-2 (IL-2), Nivolumab rescue
Adoptive transfer of Autologous Tumor-Infiltrating Lymphocytes
Cyclophosphamide will be administered as an intravenous (IV) infusion for two days.
Fludarabine will be administered as an intravenous (IV) infusion for five days.
After TIL infusion, IL-2 (optional) will be started as a bolus administration every eight hours, for a maximum of eight doses.
Nivolumab (3mg/kg) will be administered every two weeks for maximum 24 months.
- Feasibility of TIL-ACT - successful Rapid Expansion Protocol (REP) [ Time Frame: Evaluated for each patient at day 0 (5-10 days after chemotherapy start). After day 0 of the last patient, the number of patients with successful REP/ start of TIL-ACT infusion will be calculated. ]Number of patients for whom TIL cultures after REP achieve the required cell number and release criteria to start TIL-ACT infusion
- Feasibility of TIL-ACT - successful infusion [ Time Frame: Evaluated for each patient at day 0 (5-10 days after chemotherapy start), up to 60 mins after start of TIL-ACT infusion. At day 0 of the last patient, the number of patients with successful TIL-ACT infusion will be calculated. ]Number of patients receiving a complete TIL-ACT infusion (full NMA chemo and at least partial TIL infusion; no minimum IL-2 required)
- Toxicity of TIL-ACT [ Time Frame: 37 days after chemotherapy start (TLT period) ]Number of patients with adverse events as assessed by CTCAE version 4.03
- Feasibility of nivolumab rescue following TIL-ACT [ Time Frame: 6 months from nivolumab start/ 100 days after end of nivolumab treatment ]Number of patients included in the 'nivolumab rescue' population
- Toxicity of nivolumab rescue [ Time Frame: 6 months from nivolumab start/ 100 days after end of nivolumab treatment ]Number of patients receiving nivolumab with adverse events as assessed by CTCAE version 4.03
- Objective response rate (ORR) [ Time Frame: 6, 12, 24, 36, 48 and 60 months ]Best overall response
- Progression free survival (PFS) for TIL-ACT [ Time Frame: 5 years ]Time from start of NMA chemotherapy until objective tumor progression (using RECIST criteria and iRECIST) or death if not documented progression.
- Progression free survival (PFS) in the nivolumab rescue phase [ Time Frame: 5 years ]Time from start of nivolumab treatment until objective tumor progression (using RECIST criteria and iRECIST) or death if not documented progression.
- Overall survival (OS) [ Time Frame: 5 years ]Time from start of NMA chemotherapy until death
- Exploratory endpoints: immune monitoring [ Time Frame: 5 years ]Immune monitoring of the peripheral and tumor immune by Human Leukocyte Antigen (HLA) determination, immunohistochemistry, T-cell Receptor (TCR) sequencing, RNA expression and single-cell analyses, in order to correlate immune parameters in the tumor microenvironment with clinical response
- Exploratory endpoints: tumor neoangiogenesis [ Time Frame: 5 years ]Tumor neoangiogenesis using 68Ga-NODAGA-RGD PET-CT to explore correlation with clinical response
- Exploratory endpoints: tumor metabolism [ Time Frame: 5 years ]Tumor metabolism using 18FDG PET-CT to explore correlation with response to TIL-ACT
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03475134
|Contact: Lana Kandalaft, PharmD, PhDfirstname.lastname@example.org|
|CHUV Oncology Department||Recruiting|
|Lausanne, Vaud, Switzerland, 1011|
|Contact: George Coukos +41213140627 email@example.com|
|Principal Investigator:||George Coukos, MD, PhD||Department director|